3-(1h-benzo[d]imidazol-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof

ABSTRACT

Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an azaindazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.62/047,509, filed Sep. 8, 2014, which is incorporated herein byreference in its entirety.

BACKGROUND

Technical Field

This disclosure relates to inhibitors of one or more proteins in the Wntpathway, including inhibitors of one or more Wnt proteins, andcompositions comprising the same. More particularly, it concerns the useof an azaindazole compound or salts or analogs thereof, in the treatmentof disorders characterized by the activation of Wnt pathway signaling(e.g., cancer, abnormal cellular proliferation, angiogenesis, fibroticdisorders, bone or cartilage diseases, and osteoarthritis), themodulation of cellular events mediated by Wnt pathway signaling, as wellas genetic diseases and neurological conditions/disorders/diseases dueto mutations or dysregulation of the Wnt pathway and/or of one or moreof Wnt signaling components. Also provided are methods for treatingWnt-related disease states.

Background

The Wnt growth factor family includes more than 10 genes identified inthe mouse and at least 19 genes identified in the human. Members of theWnt family of signaling molecules mediate many short- and long-rangepatterning processes during invertebrate and vertebrate development. TheWnt signaling pathway is known for its role in the inductiveinteractions that regulate growth and differentiation, and it also playsroles in the homeostatic maintenance of post-embryonic tissue integrity.Wnt stabilizes cytoplasmic β-catenin, which stimulates the expression ofgenes including c-myc, c jun, fra-1, and cyclin D1. In addition,misregulation of Wnt signaling can cause developmental defects and isimplicated in the genesis of several human cancers. The Wnt pathway hasalso been implicated in the maintenance of stem or progenitor cells in agrowing list of adult tissues including skin, blood, gut, prostate,muscle, and the nervous system.

SUMMARY

The present disclosure provides methods and reagents, involvingcontacting a cell with an agent, such as an azaindazole compound, in asufficient amount to antagonize a Wnt activity, e.g., to reverse orcontrol an aberrant growth state or correct a genetic disorder due tomutations in Wnt signaling components.

Some embodiments disclosed herein include Wnt inhibitors containing anazaindazole core. Other embodiments disclosed herein includepharmaceutical compositions and methods of treatment using thesecompounds.

One embodiment disclosed herein includes a compound having the structureof Formula I:

as well as prodrugs and pharmaceutically acceptable salts thereof.

In some embodiments of Formula (I):

R¹ is selected from the group consisting of -heteroaryl(R⁴)_(q) and-heterocyclyl(R⁵)_(h);

R² is selected from the group consisting of H and halide;

R³ is selected from the group consisting of H, -heteroaryl(R⁶)_(q),-heterocyclyl(R⁷)_(h), and -aryl(R⁸)_(k);

each R⁴ is one substituent attached to the heteroaryl and isindependently selected from the group consisting of halide, —(C₁₋₆alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R⁹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹¹)_(k),—NHC(═O)R¹², —NR¹³R¹⁴, —(C₁₋₆ alkylene)NR¹⁵R¹⁶, and —OR²²;

each R⁵ is one substituent attached to the heterocyclyl and isindependently selected from the group consisting of —(C₁₋₄ alkyl),halide, —CF₃, and —CN;

each R⁶ is one substituent attached to the heteroaryl and isindependently selected from the group consisting of —(C₁₋₆ alkyl),halide, —CF₃, —OCH₃, —CN, and —C(═O)R¹⁷;

each R⁷ is one substituent attached to the heterocyclyl and isindependently selected from the group consisting of —(C₁₋₆ alkyl),halide, —CF₃, —CN, and —OCH₃;

each R⁸ is one substituent attached to the aryl and is independentlyselected from the group consisting of —(C₁₋₆ alkyl), halide, —CF₃, —CN,—OCH₃, —(C₁₋₆ alkylene)_(p)NHSO₂R¹⁷, —NR¹³(C₁₋₆ alkylene)NR¹³R¹⁴,alkylene)_(p)NR¹³R¹⁴, and —OR²⁵;

each R⁹ is one substituent attached to the heterocyclyl and isindependently selected from the group consisting of amino, —(C₁₋₄alkyl), halide, —CF₃, and —CN;

each R¹⁰ is one substituent attached to the carbocyclyl and isindependently selected from the group consisting of —(C₁₋₄ alkyl),halide, —CF₃, and —CN;

each R¹¹ is one substituent attached to the aryl and is independentlyselected from the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and—CN;

each R¹² is independently selected from the group consisting of —(C₁₋₉alkyl), -heteroaryl(R¹⁸)_(q), -aryl(R¹⁹)_(k), —CH₂aryl(R¹⁹)_(k),-carbocyclyl(R²⁰)_(j), —CH₂carbocyclyl(R²⁰)_(j), —(C₁₋₄alkylene)_(p)NR²³R²⁴, -heterocyclyl(R²¹)_(h), and—CH₂heterocyclyl(R²¹)_(h);

each R¹³ is independently selected from the group consisting of H and—(C₁₋₆ alkyl);

each R¹⁴ is independently selected from the group consisting of H,—(C₁₋₆ alkyl), —CH₂aryl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j);

each R¹⁵ is independently selected from the group consisting of H and—(C₁₋₆ alkyl);

each R¹⁶ is independently selected from the group consisting of H,—(C₁₋₆ alkyl), —CH₂aryl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j);

each R¹⁷ is a —(C₁₋₆ alkyl);

each R¹⁸ is one substituent attached to the heteroaryl and isindependently selected from the group consisting of —(C₁₋₄ alkyl),halide, —CF₃, and —CN;

each R¹⁹ is one substituent attached to the aryl and is independentlyselected from the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and—CN;

each R²⁰ is one substituent attached to the carbocyclyl and isindependently selected from the group consisting of —(C₁₋₄ alkyl),halide, —CF₃, and —CN;

each R²¹ is one substituent attached to the heterocyclyl and isindependently selected from the group consisting of —(C₁₋₄ alkyl),halide, —CF₃, and —CN;

each R²² is independently selected from the group consisting of H,—(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R²¹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R²⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹⁹)_(k),and —(C₁₋₆ alkylene)_(p)NR²³R²⁴;

each R²³ is independently selected from the group consisting of H and—(C₁₋₆ alkyl);

each R²⁴ is independently selected from the group consisting of H and—(C₁₋₆ alkyl);

each R²⁵ is independently selected from the group consisting of H,—(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R²¹)_(h), and —(C₁₋₆alkylene)_(p)NR²³R²⁴;

each p is independently 0 or 1;

each q is independently 0 to 4;

each h is independently 0 to 10;

each k is independently 0 to 5; and

each j is independently 0 to 12.

Some embodiments include stereoisomers and pharmaceutically acceptablesalts of a compound of Formula (I).

Some embodiments include pro-drugs of a compound of Formula (I).

Some embodiments of the present disclosure include pharmaceuticalcompositions comprising a compound of Formula (I) and a pharmaceuticallyacceptable carrier, diluent, or excipient.

Other embodiments disclosed herein include methods of inhibiting one ormore members of the Wnt pathway, including one or more Wnt proteins byadministering to a patient affected by a disorder or disease in whichaberrant Wnt signaling is implicated, such as cancer and other diseasesassociated with abnormal angiogenesis, cellular proliferation, cellcycling and mutations in Wnt signaling components, a compound accordingto Formula (I). Accordingly, the compounds and compositions providedherein can be used to treat cancer, to reduce or inhibit angiogenesis,to reduce or inhibit cellular proliferation and correct a geneticdisorder due to mutations in Wnt signaling components.

Non-limiting examples of diseases which can be treated with thecompounds and compositions provided herein include a variety of cancers,diabetic retinopathy, pulmonary fibrosis, rheumatoid arthritis, sepsis,ankylosing spondylitis, psoriasis, scleroderma, mycotic and viralinfections, osteochondrodysplasia, Alzheimer's disease, lung disease,bone/osteoporotic (wrist, spine, shoulder and hip) fractures, articularcartilage (chondral) defects, degenerative disc disease (orintervertebral disc degeneration), polyposis coli,osteoporosis-pseudoglioma syndrome, familial exudativevitreoretinopathy, retinal angiogenesis, early coronary disease,tetra-Amelia syndrome, Müllerian-duct regression and virilization,SERKAL syndrome, diabetes mellitus type 2, Fuhrmann syndrome,Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,odonto-onycho-dermal dysplasia, obesity, split-hand/foot malformation,caudal duplication syndrome, tooth agenesis, Wilms tumor, skeletaldysplasia, focal dermal hypoplasia, autosomal recessive anonychia,neural tube defects, alpha-thalassemia (ATRX) syndrome, fragile Xsyndrome, ICF syndrome, Angelman syndrome, Prader-Willi syndrome,Beckwith-Wiedemann Syndrome, Norrie disease, and Rett syndrome.

Some embodiments of the present disclosure include methods to preparecompounds of Formula (I).

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the invention, as claimed.

DETAILED DESCRIPTION

Provided herein are compositions and methods for inhibiting one or moremembers of the Wnt pathway, including one or more Wnt proteins. OtherWnt inhibitors and methods for using the same are disclosed in U.S.application Ser. Nos. 12/852,706; 12/968,505; 13/552,188; 13/800,963;13/855,874; 13/887,177 13/938,691; 13/938,692; 14/019,103; 14/019,147;14/019,940; 14/149,948; 14/178,749; 14/331,427; and Ser. No. 14/334,005;and U.S. Provisional Application Ser. Nos. 61/232,603; 61/288,544;61/305,459; 61/620,107; 61/642,915; and 61/750,221, all of which areincorporated by reference in their entirety herein.

Some embodiments provided herein relate to a method for treating adisease or disorder including, but not limited to, cancers, diabeticretinopathy, pulmonary fibrosis, rheumatoid arthritis, sepsis,ankylosing spondylitis, psoriasis, scleroderma, mycotic and viralinfections, bone and cartilage diseases, Alzheimer's disease, lungdisease, osteoarthritis, bone/osteoporotic (wrist, spine, shoulder andhip) fractures, articular cartilage (chondral) defects, degenerativedisc disease (or intervertebral disc degeneration), polyposis coli, bonedensity and vascular defects in the eye (Osteoporosis-pseudogliomaSyndrome, OPPG) and other eye diseases or syndromes associated withdefects or damaged photoreceptors, familial exudative vitreoretinopathy,retinal angiogenesis, early coronary disease, tetra-amelia,Müllerian-duct regression and virilization, SERKAL syndrome, type IIdiabetes, Fuhrmann syndrome, Al-Awadi/Raas-Rothschild/Schinzelphocomelia syndrome, odonto-onycho-dermal dysplasia, obesity,split-hand/foot malformation, caudal duplication, tooth agenesis, Wilmstumor, skeletal dysplasia, focal dermal hypoplasia, autosomal recessiveanonychia, neural tube defects, alpha-thalassemia (ATRX) syndrome,fragile X syndrome, ICF syndrome, Angelman's syndrome, Prader-Willisyndrome, Beckwith-Wiedemann Syndrome, Norrie disease, and Rettsyndrome.

In some embodiments, non-limiting examples of bone and cartilagediseases which can be treated with the compounds and compositionsprovided herein include bone spur (osteophytes), craniosynostosis,fibrodysplasia ossificans progressive, fibrous dysplasia, giant celltumor of bone, hip labral tear, meniscal tears, bone/osteoporotic(wrist, spine, shoulder and hip) fractures, articular cartilage(chondral) defects, degenerative disc disease (or intervertebral discdegeneration), osteochondritis dissecans, osteochondroma (bone tumor),osteopetrosis, relapsing polychondritis, and Salter-Harris fractures.

In some embodiments, pharmaceutical compositions are provided that areeffective for treatment of a disease of an animal, e.g., a mammal,caused by the pathological activation or mutations of the Wnt pathway.The composition includes a pharmaceutically acceptable carrier and acompound as described herein.

Definitions

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as is commonly understood by one of ordinary skillin the art to which this disclosure belongs. All patents, applications,published applications, and other publications are incorporated byreference in their entirety. In the event that there is a plurality ofdefinitions for a term herein, those in this section prevail unlessstated otherwise.

As used herein, “alkyl” means a branched, or straight chain chemicalgroup containing only carbon and hydrogen, such as methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, sec-pentyl and neo-pentyl. Alkyl groups can eitherbe unsubstituted or substituted with one or more substituents. Alkylgroups can be saturated or unsaturated (e.g., containing —C═C— or —C≡C—subunits), at one or several positions. In some embodiments, alkylgroups include 1 to 9 carbon atoms (for example, 1 to 6 carbon atoms, 1to 4 carbon atoms, or 1 to 2 carbon atoms).

As used herein, “alkylene” means a bivalent branched, or straight chainchemical group containing only carbon and hydrogen, such as methylene,ethylene, n-propylene, iso-propylene, n-butylene, iso-butylene,sec-butylene, tert-butylene, n-pentylene, iso-pentylene, sec-pentyleneand neo-pentylene. Alkylene groups can either be unsubstituted orsubstituted with one or more substituents. Alkylene groups can besaturated or unsaturated (e.g., containing —C═C— or —C≡C— subunits), atone or several positions. In some embodiments, alkylene groups include 1to 9 carbon atoms (for example, 1 to 6 carbon atoms, 1 to 4 carbonatoms, or 1 to 2 carbon atoms).

As used herein, “carbocyclyl” means a cyclic ring system containing onlycarbon atoms in the ring system backbone, such as cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, and cyclohexenyl. Carbocyclyls mayinclude multiple fused rings. Carbocyclyls may have any degree ofsaturation provided that at least one ring in the ring system is notaromatic. Carbocyclyl groups can either be unsubstituted or substitutedwith one or more substituents. In some embodiments, carbocyclyl groupsinclude 3 to 10 carbon atoms, for example, 3 to 6 carbon atoms.

As used herein, “lower alkyl” means a subset of alkyl having 1 to 3carbon atoms, which is linear or branched. Examples of lower alkylsinclude methyl, ethyl, n-propyl and isopropyl. Likewise, radicals usingthe terminology “lower” refer to radicals having 1 to about 3 carbons inthe alkyl portion of the radical.

As used herein, “aryl” means a mono-, bi-, tri- or polycyclic group withonly carbon atoms present in the ring backbone having 5 to 14 ringatoms, alternatively 5, 6, 9, or 10 ring atoms; and having 6, 10, or 14pi electrons shared in a cyclic array; wherein at least one ring in thesystem is aromatic. Aryl groups can either be unsubstituted orsubstituted with one or more substituents. Examples of aryl includephenyl, naphthyl, tetrahydronaphthyl, 2,3-dihydro-1H-indenyl, andothers. In some embodiments, the aryl is phenyl.

As used herein, “arylalkyl” means an aryl-alkyl-group in which the aryland alkyl moieties are as previously described. In some embodiments,arylalkyl groups contain a C₁₋₄alkyl moiety. Exemplary arylalkyl groupsinclude benzyl and 2-phenethyl.

As used herein, the term “heteroaryl” means a mono-, bi-, tri- orpolycyclic group having 5 to 14 ring atoms, alternatively 5, 6, 9, or 10ring atoms; and having 6, 10, or 14 pi electrons shared in a cyclicarray; wherein at least one ring in the system is aromatic, and at leastone ring in the system contains one or more heteroatoms independentlyselected from the group consisting of N, O, and S. Heteroaryl groups caneither be unsubstituted or substituted with one or more substituents.Examples of heteroaryl include thienyl, pyridinyl, furyl, oxazolyl,oxadiazolyl, pyrrolyl, imidazolyl, triazolyl, thiodiazolyl, pyrazolyl,isoxazolyl, thiadiazolyl, pyranyl, pyrazinyl, pyrimidinyl, pyridazinyl,triazinyl, thiazolyl benzothienyl, benzoxadiazolyl, benzofuranyl,benzimidazolyl, benzotriazolyl, cinnolinyl, indazolyl, indolyl,isoquinolinyl, isothiazolyl, naphthyridinyl, purinyl, thienopyridinyl,pyrido[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyridinyl, quinazolinyl,quinolinyl, thieno[2,3-c]pyridinyl, pyrazolo[3,4-b]pyridinyl,pyrazolo[3,4-c]pyridinyl, pyrazolo[4,3-c]pyridine,pyrazolo[4,3-b]pyridinyl, tetrazolyl, chromane,2,3-dihydrobenzo[b][1,4]dioxine, benzo[d][1,3]dioxole,2,3-dihydrobenzofuran, 2,3-dihydrobenzo[b][1,4]oxathiine, and others. Insome embodiments, the heteroaryl is selected from thienyl, pyridinyl,furyl, pyrazolyl, imidazolyl, pyranyl, pyrazinyl, and pyrimidinyl.

As used herein, “halo”, “halide” or “halogen” is a chloro, bromo,fluoro, or iodo atom radical. In some embodiments, a halo is a chloro,bromo or fluoro. For example, a halide can be fluoro.

As used herein, “haloalkyl” means a hydrocarbon substituent, which is alinear or branched, alkyl, alkenyl or alkynyl substituted with one ormore chloro, bromo, fluoro, and/or iodo atom(s). In some embodiments, ahaloalkyl is a fluoroalkyls, wherein one or more of the hydrogen atomshave been substituted by fluoro. In some embodiments, haloalkyls are of1 to about 3 carbons in length (e.g., 1 to about 2 carbons in length or1 carbon in length). The term “haloalkylene” means a diradical variantof haloalkyl, and such diradicals may act as spacers between radicals,other atoms, or between a ring and another functional group.

As used herein, “heterocyclyl” means a nonaromatic cyclic ring systemcomprising at least one heteroatom in the ring system backbone.Heterocyclyls may include multiple fused rings. Heterocyclyls may besubstituted or unsubstituted with one or more substituents. In someembodiments, heterocycles have 5-7 members. In six membered monocyclicheterocycles, the heteroatom(s) are selected from one to three of O, Nor S, and wherein when the heterocycle is five membered, it can have oneor two heteroatoms selected from O, N, or S. Examples of heterocyclylinclude azirinyl, aziridinyl, azetidinyl, oxetanyl, thietanyl,1,4,2-dithiazolyl, dihydropyridinyl, 1,3-dioxanyl, 1,4-dioxanyl,1,3-dioxolanyl, morpholinyl, thiomorpholinyl, piperazinyl, pyranyl,pyrrolidinyl, tetrahydrofuryl, tetrahydropyridinyl, oxazinyl, thiazinyl,thiinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isoxazolidinyl,piperidinyl, pyrazolidinyl imidazolidinyl, thiomorpholinyl, and others.In some embodiments, the heterocyclyl is selected from azetidinyl,morpholinyl, piperazinyl, pyrrolidinyl, and tetrahydropyridinyl.

As used herein, “monocyclic heterocyclyl” means a single nonaromaticcyclic ring comprising at least one heteroatom in the ring systembackbone. Heterocyclyls may be substituted or unsubstituted with one ormore substituents. In some embodiments, heterocycles have 5-7 members.In six membered monocyclic heterocycles, the heteroatom(s) are selectedfrom one to three of O, N or S, and wherein when the heterocycle is fivemembered, it can have one or two heteroatoms selected from O, N, or S.Examples of heterocyclyl include azirinyl, aziridinyl, azetidinyl,oxetanyl, thietanyl, 1,4,2-dithiazolyl, dihydropyridinyl, 1,3-dioxanyl,1,4-dioxanyl, 1,3-dioxolanyl, morpholinyl, thiomorpholinyl, piperazinyl,pyranyl, pyrrolidinyl, tetrahydrofuryl, tetrahydropyridinyl, oxazinyl,thiazinyl, thiinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl,isoxazolidinyl, piperidinyl, pyrazolidinyl imidazolidinyl,thiomorpholinyl, and others.

The term “substituted” refers to moieties having substituents replacinga hydrogen on one or more non-hydrogen atoms of the molecule. It will beunderstood that “substitution” or “substituted with” includes theimplicit proviso that such substitution is in accordance with permittedvalence of the substituted atom and the substituent, and that thesubstitution results in a stable compound, e.g., which does notspontaneously undergo transformation such as by rearrangement,cyclization, elimination, etc. Substituents can include, for example,—(C₁₋₉ alkyl) optionally substituted with one or more of hydroxyl, —NH₂,—NH(C₁₋₃ alkyl), and —N(C₁₋₃ alkyl)₂; —(C₁₋₉ haloalkyl); a halide; ahydroxyl; a carbonyl [such as —C(O)OR, and —C(O)R]; a thiocarbonyl [suchas —C(S)OR, —C(O)SR, and —C(S)R]; —(C₁₋₉ alkoxyl) optionally substitutedwith one or more of halide, hydroxyl, —NH₂, —NH(C₁₋₃ alkyl), and —N(C₁₋₃alkyl)₂; —OPO(OH)₂; a phosphonate [such as —PO(OH)₂ and —PO(OR′)₂];—OPO(OR′)R″; —NRR′; —C(O)NRR′; —C(NR)NR′R″; —C(NR′)R″; a cyano; a nitro;an azido; —SH; —S—R; —OSO₂(OR); a sulfonate [such as —SO₂(OH) and—SO₂(OR)]; —SO₂NR′R″; and —SO₂R; in which each occurrence of R, R′ andR″ are independently selected from H; —(C₁₋₉ alkyl); C₆₋₁₀ aryloptionally substituted with from 1-3R′″; 5-10 membered heteroaryl havingfrom 1-4 heteroatoms independently selected from N, O, and S andoptionally substituted with from 1-3 R′″; C₃₋₇ carbocyclyl optionallysubstituted with from 1-3 R′″; and 3-8 membered heterocyclyl having from1-4 heteroatoms independently selected from N, O, and S and optionallysubstituted with from 1-3 R′″; wherein each R′″ is independentlyselected from —(C₁₋₆ alkyl), —(C₁₋₆ haloalkyl), a halide (e.g., F), ahydroxyl, —C(O)OR, —C(O)R, —(C₁₋₆ alkoxyl), —NRR′, —C(O)NRR′, and acyano, in which each occurrence of R and R′ is independently selectedfrom H and —(C₁₋₆ alkyl). In some embodiments, the substituent isselected from —(C₁₋₆ alkyl), —(C₁₋₆ haloalkyl), a halide (e.g., F), ahydroxyl, —C(O)OR, —C(O)R, —(C₁₋₆ alkoxyl), —NRR′, —C(O)NRR′, and acyano, in which each occurrence of R and R′ is independently selectedfrom H and —(C₁₋₆ alkyl).

As used herein, when two groups are indicated to be “linked” or “bonded”to form a “ring”, it is to be understood that a bond is formed betweenthe two groups and may involve replacement of a hydrogen atom on one orboth groups with the bond, thereby forming a carbocyclyl, heterocyclyl,aryl, or heteroaryl ring. The skilled artisan will recognize that suchrings can and are readily formed by routine chemical reactions. In someembodiments, such rings have from 3-7 members, for example, 5 or 6members.

The skilled artisan will recognize that some structures described hereinmay be resonance forms or tautomers of compounds that may be fairlyrepresented by other chemical structures, even when kinetically, theartisan recognizes that such structures are only a very small portion ofa sample of such compound(s). Such compounds are clearly contemplatedwithin the scope of this disclosure, though such resonance forms ortautomers are not represented herein.

The compounds provided herein may encompass various stereochemicalforms. The compounds also encompass diastereomers as well as opticalisomers, e.g., mixtures of enantiomers including racemic mixtures, aswell as individual enantiomers and diastereomers, which arise as aconsequence of structural asymmetry in certain compounds. Separation ofthe individual isomers or selective synthesis of the individual isomersis accomplished by application of various methods which are well knownto practitioners in the art. Unless otherwise indicated, when adisclosed compound is named or depicted by a structure withoutspecifying the stereochemistry and has one or more chiral centers, it isunderstood to represent all possible stereoisomers of the compound.

The term “administration” or “administering” refers to a method ofproviding a dosage of a compound or pharmaceutical composition to avertebrate or invertebrate, including a mammal, a bird, a fish, or anamphibian, where the method is, e.g., orally, subcutaneously,intravenously, intralymphatic, intranasally, topically, transdermally,intraperitoneally, intramuscularly, intrapulmonarilly, vaginally,rectally, ontologically, neuro-otologically, intraocularly,subconjuctivally, via anterior eye chamber injection, intravitreally,intraperitoneally, intrathecally, intracystically, intrapleurally, viawound irrigation, intrabuccally, intra-abdominally, intra-articularly,intra-aurally, intrabronchially, intracapsularly, intrameningeally, viainhalation, via endotracheal or endobronchial instillation, via directinstillation into pulmonary cavities, intraspinally, intrasynovially,intrathoracically, via thoracostomy irrigation, epidurally,intratympanically, intracisternally, intravascularly,intraventricularly, intraosseously, via irrigation of infected bone, orvia application as part of any admixture with a prosthetic device. Themethod of administration can vary depending on various factors, e.g.,the components of the pharmaceutical composition, the site of thedisease, the disease involved, and the severity of the disease.

A “diagnostic” as used herein is a compound, method, system, or devicethat assists in the identification or characterization of a health ordisease state. The diagnostic can be used in standard assays as is knownin the art.

The term “mammal” is used in its usual biological sense. Thus, itspecifically includes humans, cattle, horses, monkeys, dogs, cats, mice,rats, cows, sheep, pigs, goats, and non-human primates, but alsoincludes many other species.

The term “pharmaceutically acceptable carrier”, “pharmaceuticallyacceptable diluent” or “pharmaceutically acceptable excipient” includesany and all solvents, co-solvents, complexing agents, dispersion media,coatings, isotonic and absorption delaying agents and the like which arenot biologically or otherwise undesirable. The use of such media andagents for pharmaceutically active substances is well known in the art.Except insofar as any conventional media or agent is incompatible withthe active ingredient, its use in the therapeutic compositions iscontemplated. Supplementary active ingredients can also be incorporatedinto the compositions. In addition, various adjuvants such as arecommonly used in the art may be included. These and other such compoundsare described in the literature, e.g., in the Merck Index, Merck &Company, Rahway, N.J. Considerations for the inclusion of variouscomponents in pharmaceutical compositions are described, e.g., in Gilmanet al. (Eds.) (2010); Goodman and Gilman's: The Pharmacological Basis ofTherapeutics, 12th Ed., The McGraw-Hill Companies.

The term “pharmaceutically acceptable salt” refers to salts that retainthe biological effectiveness and properties of the compounds providedherein and, which are not biologically or otherwise undesirable. In manycases, the compounds provided herein are capable of forming acid and/orbase salts by virtue of the presence of amino and/or carboxyl groups orgroups similar thereto. Many such salts are known in the art, forexample, as described in WO 87/05297. Pharmaceutically acceptable acidaddition salts can be formed with inorganic acids and organic acids.Inorganic acids from which salts can be derived include, for example,hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid,phosphoric acid, and the like. Organic acids from which salts can bederived include, for example, acetic acid, propionic acid, glycolicacid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinicacid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamicacid, mandelic acid, methanesulfonic acid, ethanesulfonic acid,p-toluenesulfonic acid, salicylic acid, and the like. Pharmaceuticallyacceptable base addition salts can be formed with inorganic and organicbases. Inorganic bases from which salts can be derived include, forexample, sodium, potassium, lithium, ammonium, calcium, magnesium, iron,zinc, copper, manganese, aluminum, and the like; particularly preferredare the ammonium, potassium, sodium, calcium, and magnesium salts.Organic bases from which salts can be derived include, for example,primary, secondary, and tertiary amines, substituted amines includingnaturally occurring substituted amines, cyclic amines, basic ionexchange resins, and the like, specifically such as isopropylamine,trimethylamine, diethylamine, triethylamine, tripropylamine, andethanolamine.

“Solvate” refers to the compound formed by the interaction of a solventand a compound as provided herein or a salt thereof. Suitable solvatesare pharmaceutically acceptable solvates including hydrates.

“Patient” as used herein, means a human or a non-human mammal, e.g., adog, a cat, a mouse, a rat, a cow, a sheep, a pig, a goat, a non-humanprimate, or a bird, e.g., a chicken, as well as any other vertebrate orinvertebrate. In some embodiments, the patient is a human.

A “therapeutically effective amount” or “pharmaceutically effectiveamount” of a compound as provided herein is one which is sufficient toachieve the desired physiological effect and may vary according to thenature and severity of the disease condition, and the potency of thecompound. “Therapeutically effective amount” is also intended to includeone or more of the compounds of Formula I in combination with one ormore other agents that are effective to treat the diseases and/orconditions described herein. The combination of compounds can be asynergistic combination. Synergy, as described, for example, by Chou andTalalay, Advances in Enzyme Regulation (1984), 22, 27-55, occurs whenthe effect of the compounds when administered in combination is greaterthan the additive effect of the compounds when administered alone as asingle agent. In general, a synergistic effect is most clearlydemonstrated at sub-optimal concentrations of the compounds. It will beappreciated that different concentrations may be employed forprophylaxis than for treatment of an active disease. This amount canfurther depend upon the patient's height, weight, sex, age and medicalhistory.

A therapeutic effect relieves, to some extent, one or more of thesymptoms of the disease.

“Treat,” “treatment,” or “treating,” as used herein refers toadministering a compound or pharmaceutical composition as providedherein for therapeutic purposes. The term “therapeutic treatment” refersto administering treatment to a patient already suffering from a diseasethus causing a therapeutically beneficial effect, such as amelioratingexisting symptoms, ameliorating the underlying metabolic causes ofsymptoms, postponing or preventing the further development of adisorder, and/or reducing the severity of symptoms that will or areexpected to develop.

“Drug-eluting” and/or controlled release as used herein refers to anyand all mechanisms, e.g., diffusion, migration, permeation, and/ordesorption by which the drug(s) incorporated in the drug-elutingmaterial pass therefrom over time into the surrounding body tissue.

“Drug-eluting material” and/or controlled release material as usedherein refers to any natural, synthetic or semi-synthetic materialcapable of acquiring and retaining a desired shape or configuration andinto which one or more drugs can be incorporated and from whichincorporated drug(s) are capable of eluting over time.

“Elutable drug” as used herein refers to any drug or combination ofdrugs having the ability to pass over time from the drug-elutingmaterial in which it is incorporated into the surrounding areas of thebody.

The term “comprising” as used herein is synonymous with “including,”“containing,” or “characterized by,” and is inclusive or open-ended anddoes not exclude additional, unrecited elements or method steps.

Compounds

The compounds and compositions described herein can be used asanti-proliferative agents, e.g., anti-cancer and anti-angiogenesisagents, and/or as inhibitors of the Wnt signaling pathway, e.g., fortreating diseases or disorders associated with aberrant Wnt signaling.In addition, the compounds can be used as inhibitors of one or morekinases, kinase receptors, or kinase complexes. Such compounds andcompositions are also useful for controlling cellular proliferation,differentiation, and/or apoptosis.

Some embodiments of the present disclosure include compounds of FormulaI:

or salts, pharmaceutically acceptable salts, or prodrugs thereof.

In some embodiments, R¹ is selected from the group consisting of-pyridinyl(R⁴) and -pyrimidinyl(R⁵).

In some embodiments, R¹ is selected from the group consisting of-heteroaryl(R⁴)_(q) and -heterocyclyl(R⁵)_(h).

In some embodiments, R¹ is selected from the group consisting of-piperidinyl(R⁵)_(h) and -tetrahydropyridinyl(R⁵)_(h).

In some embodiments, R¹ is selected from the group consisting of-pyridinyl(R⁴)_(q), -pyrimidinyl(R⁴)_(q), -pyrazinyl(R⁴)_(q),-pyrazolyl(R⁴)_(q), and -imidazolyl(R⁴)_(q).

In some embodiments, R² is selected from the group consisting of H andhalide.

In some embodiments, R³ is selected from the group consisting of-heteroaryl(R⁶)_(q), -heterocyclyl(R⁷)_(h), and -aryl(R⁸)_(k).

In some embodiments, R³ is selected from the group consisting of H,-heteroaryl(R⁶)_(q), -heterocyclyl(R⁷)_(h), and -aryl(R⁸)_(k).

In some embodiments, R³ is selected from the group consisting of-pyridinyl(R⁶)_(q), -imidazolyl(R⁶)_(q), -furanyl(R⁶)_(q),-thiophenyl(R⁶)_(q), -piperidinyl(R⁷)_(h), -piperazinyl(R⁷)_(h), and-phenyl(R⁸)_(k).

In some embodiments, R⁴ is one substituent attached to the pyridinyl andis selected from the group consisting of H, halide, —(C₁₋₆ alkyl),—(C₁₋₄ alkylene)_(p)heterocyclyl(R⁹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹¹)_(k),—NHC(═O)R¹², —NR¹³R¹⁴ and —(C₁₋₆ alkylene)NR¹⁵R¹⁶.

In some embodiments, each R⁴ is one substituent attached to theheteroaryl and is independently selected from the group consisting ofhalide, —(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R⁹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹¹)_(k),—NHC(═O)R¹², —NR¹³R¹⁴, —(C₁₋₆ alkylene)NR¹⁵R¹⁶, and —OR²².

In some embodiments, each R⁴ is one substituent attached to theheteroaryl and is independently selected from the group consisting of F,-Me, -Et, —(CH₂)heterocyclyl(R⁹)_(h), -heterocyclyl(R⁹)_(h),—(CH₂)carbocyclyl(R¹⁰)_(j), —(CH₂)aryl(R¹¹)_(k), —NHC(═O)(C₁₋₅ alkyl),—NHC(═O)phenyl(R¹⁹)_(k), —NHC(═O)(CH₂)phenyl(R¹⁹)_(k),—NHC(═O)carbocyclyl(R²⁰)_(j), —NHC(═O)(CH₂)heterocyclyl(R²¹)_(h), —NH₂,—N(C₁₋₃ alkyl)₂, —NH(C₁₋₄ alkyl), —(CH₂)N(C₁₋₃ alkyl)₂, —(CH₂)NH(C₁₋₄alkyl), —OH, —O(C₁₋₃ alkyl), -Ocarbocyclyl(R²⁰)_(j),-Oheterocyclyl(R²¹)_(h), —O(CH₂CH₂)heterocyclyl(R²¹)_(h),—O(CH₂CH₂)N(C₁₋₃ alkyl)₂, and —O(CH₂)phenyl(R¹⁹)_(k).

In some embodiments, R⁵ is one substituent attached to the pyrimidinyland is selected from the group consisting of H, halide, —(C₁₋₆ alkyl),—(C₁₋₄ alkylene)_(p)heterocyclyl(R⁹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹¹)_(k),—NHC(═O)R¹², —NR¹³R¹⁴, and —(C₁₋₆ alkylene)NR¹⁵R¹⁶.

In some embodiments, each R⁵ is one substituent attached to theheterocyclyl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R⁶ is one substituent attached to theheteroaryl and is independently selected from the group consisting of H,—(C₁₋₆ alkyl), halide, —CF₃, —OCH₃, —CN, and —C(═O)R¹⁷.

In some embodiments, each R⁶ is one substituent attached to theheteroaryl and is independently selected from the group consisting of—(C₁₋₆ alkyl), halide, —CF₃, —OCH₃, —CN, and —C(═O)R¹⁷.

In some embodiments, each R⁶ is one substituent attached to theheteroaryl and is independently selected from the group consisting of-Me, -Et, F, —CF₃, —OCH₃, —CN, and —C(═O)(C₁₋₃ alkyl).

In some embodiments, each R⁷ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofH, —(C₁₋₆ alkyl), halide, —CF₃, —CN, and —OCH₃.

In some embodiments, each R⁷ is one substituent attached to theheterocyclyl and is independently selected from the group consisting of—(C₁₋₆ alkyl), halide, —CF₃, —CN, and —OCH₃.

In some embodiments, each R⁸ is one substituent attached to the aryl andis independently selected from the group consisting of H, —(C₁₋₆ alkyl),halide, —CF₃, —CN, —OCH₃, —(C₁₋₆ alkylene)_(p)NHSO₂R¹⁷, —NR¹³(C₁₋₆alkylene)NR¹³R¹⁴, and —(C₁₋₆ alkylene)_(p)NR¹³R¹⁴.

In some embodiments, each R⁸ is one substituent attached to the aryl andis independently selected from the group consisting of —(C₁₋₆ alkyl),halide, —CF₃, —CN, —OCH₃, —(C₁₋₆ alkylene)_(p)NHSO₂R¹⁷, —NR¹³(C₁₋₆alkylene)NR¹³R¹⁴, —(C₁₋₆ alkylene)_(p)NR¹³R¹⁴, and —OR²⁵.

In some embodiments, each R⁸ is one substituent attached to the aryl andis independently selected from the group consisting of -Me, -Et, F,—CF₃, —CN, —OCH₃, —(CH₂CH₂)NHSO₂(C₁₋₃ alkyl), —NH(CH₂CH₂)N(C₁₋₃ alkyl)₂,—OH, —O(C₁₋₃ alkyl), —O(CH₂CH₂)heterocyclyl(R²¹)_(h), and—O(CH₂CH₂)N(C₁₋₃ alkyl)₂.

In some embodiments, each R⁹ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofH, —(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R⁹ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofamino, —(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R⁹ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofamino, Me, Et, F, Cl, and —CF₃.

In some embodiments, each R¹⁰ is one substituent attached to thecarbocyclyl and is independently selected from the group consisting ofH, —(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹⁰ is one substituent attached to thecarbocyclyl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹⁰ is one substituent attached to thecarbocyclyl and is independently selected from the group consisting ofMe, Et, F, Cl, and —CF₃.

In some embodiments, each R¹¹ is one substituent attached to the aryland is independently selected from the group consisting of H, —(C₁₋₄alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹¹ is one substituent attached to the aryland is independently selected from the group consisting of —(C₁₋₄alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹¹ is one substituent attached to the aryland is independently selected from the group consisting of Me, Et, F,Cl, and —CF₃.

In some embodiments, each R¹² is independently selected from the groupconsisting of —(C₁₋₉ alkyl), -heteroaryl(R¹⁸)_(q), -aryl(R¹⁹)_(k),—CH₂aryl(R¹⁹)_(k), -carbocyclyl(R²⁰)_(j), and —CH₂carbocyclyl(R²⁰)_(j).

In some embodiments, each R¹² is independently selected from the groupconsisting of —(C₁₋₉ alkyl), -heteroaryl(R¹⁸)_(q), -aryl(R¹⁹)_(k),—CH₂aryl(R¹⁹)_(k), -carbocyclyl(R²⁰)_(j), —CH₂carbocyclyl(R²⁰)_(j),—(C₁₋₄ alkylene)_(p)NR²³R²⁴, -heterocyclyl(R²¹)_(h), and—CH₂heterocyclyl(R²¹)_(h).

In some embodiments, each R¹² is independently selected from the groupconsisting of —(C₁₋₅ alkyl), -phenyl(R¹⁹)_(k), —(CH₂)phenyl(R¹⁹)_(k),-carbocyclyl(R²⁰)_(j), —(CH₂)carbocyclyl(R²⁰)_(j), —(CH₂)N(C₁₋₃ alkyl)₂,and —(CH₂)heterocyclyl(R²¹)_(h).

In some embodiments, each R¹³ is independently selected from the groupconsisting of H and —(C₁₋₆ alkyl).

In some embodiments, each R¹³ is independently selected from the groupconsisting of H and —(C₁₋₃ alkyl).

In some embodiments, each R¹⁴ is independently selected from the groupconsisting of H, —(C₁₋₆ alkyl), —CH₂aryl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j).

In some embodiments, each R¹⁴ is independently selected from the groupconsisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j).

In some embodiments, each R¹⁵ is independently selected from the groupconsisting of H and —(C₁₋₆ alkyl).

In some embodiments, each R¹⁵ is independently selected from the groupconsisting of H and —(C₁₋₃ alkyl).

In some embodiments, each R¹⁶ is independently selected from the groupconsisting of H, —(C₁₋₆ alkyl), —CH₂aryl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j).

In some embodiments, each R¹⁶ is independently selected from the groupconsisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j).

In some embodiments, each R¹⁷ is independently a —(C₁₋₆ alkyl).

In some embodiments, each R¹⁷ is independently a —(C₁₋₃ alkyl).

In some embodiments, each R¹⁸ is one substituent attached to theheteroaryl and is independently selected from the group consisting of H,—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹⁸ is one substituent attached to theheteroaryl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹⁸ is one substituent attached to theheteroaryl and is independently selected from the group consisting ofMe, Et, F, Cl, and —CF₃.

In some embodiments, each R¹⁹ is one substituent attached to the aryland is independently selected from the group consisting of H, —(C₁₋₄alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹⁹ is one substituent attached to the aryland is independently selected from the group consisting of —(C₁₋₄alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹⁹ is one substituent attached to the aryland is independently selected from the group consisting of Me, Et, F,Cl, and —CF₃.

In some embodiments, each R²⁰ is one substituent attached to thecarbocyclyl and is independently selected from the group consisting ofH, —(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R²⁰ is one substituent attached to thecarbocyclyl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R²⁰ is one substituent attached to thecarbocyclyl and is independently selected from the group consisting ofMe, Et, F, Cl, and —CF₃.

In some embodiments, each R²¹ is one substituent attached to theheterocyclyl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R²¹ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofMe, Et, F, Cl, and —CF₃.

In some embodiments, R²² is selected from the group consisting of H,—(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R²¹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R²⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹⁹)_(k),and —(C₁₋₆ alkylene)_(p)NR²³R²⁴.

In some embodiments, R²² is selected from the group consisting of H,-Me, -Et, -iPr, -heterocyclyl(R²¹)_(h), —(CH₂CH₂)heterocyclyl(R²¹)_(h),-carbocyclyl(R²⁰)_(j), —(CH₂)phenyl(R¹⁹)_(k), and —(CH₂CH₂)N(C₁₋₃alkyl)₂.

In some embodiments, each R²³ is independently selected from the groupconsisting of H and —(C₁₋₆ alkyl).

In some embodiments, each R²³ is independently selected from the groupconsisting of Me and Et.

In some embodiments, each R²⁴ is independently selected from the groupconsisting of H and —(C₁₋₆ alkyl).

In some embodiments, each R²⁴ is independently selected from the groupconsisting of Me and Et.

In some embodiments, R²⁵ is selected from the group consisting of H,—(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R²¹)_(h), and —(C₁₋₆alkylene)_(p)NR²³R²⁴.

In some embodiments, R²⁵ is selected from the group consisting of H,-Me, -Et, -iPr, —(CH₂CH₂)heterocyclyl(R²¹)_(h), and —(CH₂CH₂)N(C₁₋₃alkyl)₂.

In some embodiments, each p is independently 0 or 1.

In some embodiments, each q is independently 1 to 4.

In some embodiments, each h is independently 1 to 10.

In some embodiments, each k is independently 1 to 5.

In some embodiments, each j is independently 1 to 12.

In some embodiments, each p is independently 0 or 1; in someembodiments, each p is 0; in some embodiments, each p is 1.

In some embodiments, each q is independently 0 to 4; in someembodiments, each q is 0; in some embodiments, each q is 1; in someembodiments, each q is 2; in some embodiments, each q is 3; in someembodiments, each q is 4.

In some embodiments, each h is independently 0 to 10; in someembodiments, each h is 0; in some embodiments, each h is 1; in someembodiments, each h is 2; in some embodiments, each h is 3; in someembodiments, each h is 4.

In some embodiments, each k is independently 0 to 5; in someembodiments, each k is 0; in some embodiments, each k is 1; in someembodiments, each k is 2; in some embodiments, each k is 3.

In some embodiments, each j is independently 0 to 12; in someembodiments, each j is 0; in some embodiments, each j is 1; in someembodiments, each j is 2; in some embodiments, each j is 3; in someembodiments, each j is 4.

In some embodiments, each R⁴ is one substituent attached to theheteroaryl and is independently selected from the group consisting of—(C₁₋₃ alkyl), —CH₂heterocyclyl(R⁹)_(h), —NHC(═O)R¹², —NR¹³R¹⁴, and—CH₂NR¹⁵R¹⁶.

In some embodiments, at least one R⁹ is halide.

In some embodiments, R¹² is selected from the group consisting of —(C₁₋₅alkyl), -phenyl(R¹⁹)_(k), —CH₂phenyl(R¹⁹)_(k), and-carbocyclyl(R²⁰)_(j).

In some embodiments, R¹³ and R¹⁴ are independently selected from H and—(C₁₋₅ alkyl).

In some embodiments, R¹⁵ and R¹⁶ are independently selected from H and—(C₁₋₅ alkyl).

In some embodiments, k is 1 or 2 and each R⁸ is independently a halide.

In some embodiments, k is 2, one R⁸ is halide and the other R⁸ is—CH₂NHSO₂R¹⁷.

In some embodiments, R¹⁷ is —(C₁₋₃ alkyl).

In some embodiments, k is 2, one R⁸ is halide and the other R⁸ is—NHCH₂CH₂NR¹³R¹⁴.

In some embodiments, R¹³ and R¹⁴ are independently selected from H and—(C₁₋₃ alkyl).

In some embodiments, R³ is selected from the group consisting ofpyridinyl(R⁶)_(q), -imidazolyl(R⁶)_(q), -furanyl(R⁶)_(q), and-thiophenyl(R⁶)_(q).

In some embodiments, q is 0 or 1, R⁶ is selected from the groupconsisting of halide, —(C₁₋₃ alkyl), and —C(═O)R¹⁷, wherein R¹⁷ is—(C₁₋₂ alkyl).

In some embodiments, R³ is selected from the group consisting of-piperidinyl(R⁷)_(h) and -piperazinyl(R⁷)_(h).

In some embodiments, q is 1, and R⁷ is selected from the groupconsisting of H and —(C₁₋₃ alkyl).

In some embodiments, R² is H; in other embodiments, R² is halide, e.g.F.

In some embodiments, R¹ is -heteroaryl(R⁴)_(q).

In some embodiments, R¹ is -pyridinyl(R⁴)_(q).

In some embodiments, R¹ is -pyridin-3-yl(R⁴)_(q).

In some embodiments, R¹ is -pyrimidinyl(R⁴)_(q).

In some embodiments, R¹ is -pyrimidin-5-yl(R⁴)_(q).

In some embodiments, R¹ is -pyrimidin-5-yl(R⁴)_(q) and q is 0.

In some embodiments, R¹ is -pyrazinyl(R⁴)_(q).

In some embodiments, R¹ is -pyrazolyl(R⁴)_(q).

In some embodiments, R¹ is -pyrazol-4-yl(R⁴)_(q), q is 1, and R⁴ is Me.

In some embodiments, R¹ is -pyrazol-4-yl(R⁴)_(q) and q is 0.

In some embodiments, R¹ is -imidazolyl(R⁴)_(q).

In some embodiments, R¹ is -imidazol-5-yl(R⁴)_(q), q is 1, and R⁴ is Me.

In some embodiments, R¹ is -imidazol-5-yl(R⁴)_(q), q is 2, and both R⁴are Me.

In some embodiments, R¹ is -heterocyclyl(R⁵)_(h).

In some embodiments, R¹ is -piperidinyl(R⁵)_(h).

In some embodiments, R¹ is -piperidin-4-yl(R⁵)_(h).

In some embodiments, R¹ is -piperidin-4-yl(R⁵)_(h), and h is 0.

In some embodiments, R¹ is -tetrahydropyridinyl(R⁵)_(h).

In some embodiments, R¹ is -1,2,3,6-tetrahydropyridinyl(R⁵)_(h).

In some embodiments, R¹ is -1,2,3,6-tetrahydropyridinyl(R⁵)_(h), and his 0.

In some embodiments, R³ is H.

In some embodiments, R³ is -heteroaryl(R⁶)_(q).

In some embodiments, R³ is -heterocyclyl(R⁷)_(h).

In some embodiments, R³ is -piperidinyl(R⁷)_(h).

In some embodiments, R³ is -piperazinyl(R⁷)_(h).

In some embodiments, R³ is -morpholinyl(R⁷)_(h).

In some embodiments, R³ is -aryl(R⁸)_(k).

In some embodiments, R³ is -pyridinyl(R⁶)_(q).

In some embodiments, R³ is -pyridin-3-yl(R⁶)_(q).

In some embodiments, R³ is -pyridin-4-yl(R⁶)_(q).

In some embodiments, R³ is -pyridin-5-yl(R⁶)_(q).

In some embodiments, R³ is -pyridin-3-yl(R⁶)_(q), q is 0.

In some embodiments, R³ is -pyridin-4-yl(R⁶)_(q), q is 0.

In some embodiments, R³ is -pyridin-5-yl(R⁶)_(q), q is 0.

In some embodiments, R³ is -imidazolyl(R⁶)_(q).

In some embodiments, R³ is -imidazol-1-yl(R⁶)_(q), q is 1, and R⁶ is—(C₁₋₃ alkyl).

In some embodiments, R³ is -imidazol-1-yl(R⁶)_(q), q is 1, and R⁶ ismethyl.

In some embodiments, R³ is -furanyl(R⁶)_(q).

In some embodiments, R³ is -furan-2-yl(R⁶)_(q).

In some embodiments, R³ is -furan-2-yl(R⁶)_(q) and q is 0.

In some embodiments, R³ is -furan-3-yl(R⁶)_(q).

In some embodiments, R³ is -furan-3-yl(R⁶)_(q) and q is 0.

In some embodiments, R³ is -thiophenyl(R⁶)_(q).

In some embodiments, R³ is -thiophen-2-yl(R⁶)_(q).

In some embodiments, R³ is -thiophen-2-yl(R⁶)_(q) and q is 0.

In some embodiments, R³ is -thiophen-2-yl(R⁶)_(q), q is 1 or 2, and eachR⁶ is independently a halide.

In some embodiments, R³ is -thiophen-2-yl(R⁶)_(q), q is 1 or 2, and R⁶is F.

In some embodiments, R³ is -thiophen-2-yl(R⁶)_(q), q is 1 or 2, and eachR⁶ is independently —(C₁₋₆ alkyl).

In some embodiments, R³ is -thiophen-2-yl(R⁶)_(q), q is 1 or 2, and eachR⁶ is independently —(C₁₋₂ alkyl).

In some embodiments, R³ is -thiophen-2-yl(R⁶)_(q), q is 1 or 2, and R⁶is methyl.

In some embodiments, R³ is -thiophen-2-yl(R⁶)_(q), q is 1 or 2, and R⁶is —CF₃.

In some embodiments, R³ is -thiophen-2-yl(R⁶)_(q), q is 1 or 2, and R⁶is CN.

In some embodiments, R³ is -thiophen-2-yl(R⁶)_(q), q is 1, and R⁶ is—C(═O)R¹⁷.

In some embodiments, R³ is -thiophen-2-yl(R⁶)_(q), q is 1, R⁶ is—C(═O)R¹⁷, and R¹⁷ is —(C₁₋₆ alkyl).

In some embodiments, R³ is -thiophen-2-yl(R⁶)_(q), q is 1, R⁶ is—C(═O)R¹⁷, and R¹⁷ is —(C₁₋₄ alkyl).

In some embodiments, R³ is -thiophen-2-yl(R⁶)_(q), q is 1, R⁶ is—C(═O)R¹⁷, and R¹⁷ is —(C₁₋₂ alkyl).

In some embodiments, R³ is -thiophen-2-yl(R⁶)_(q), q is 1, R⁶ is—C(═O)R¹⁷, and R¹⁷ is methyl.

In some embodiments, R³ is -thiophen-3-yl(R⁶)_(q).

In some embodiments, R³ is -thiophen-3-yl(R⁶)_(q) and q is 0.

In some embodiments, R³ is -thiophen-3-yl(R⁶)_(q), q is 1 or 2, and eachR⁶ is independently halide.

In some embodiments, R³ is -thiophen-3-yl(R⁶)_(q), q is 1 or 2, and R⁶is F.

In some embodiments, R³ is -thiophen-3-yl(R⁶)_(q), q is 1 or 2, and eachR⁶ is independently —(C₁₋₆ alkyl).

In some embodiments, R³ is -thiophen-3-yl(R⁶)_(q), q is 1 or 2, and eachR⁶ is independently —(C₁₋₂ alkyl).

In some embodiments, R³ is -thiophen-3-yl(R⁶)_(q), q is 1 or 2, and R⁶is methyl.

In some embodiments, R³ is -thiophen-3-yl(R⁶)_(q), q is 1 or 2, and R⁶is —CF₃.

In some embodiments, R³ is -thiophen-3-yl(R⁶)_(q), q is 1 or 2, and R⁶is CN.

In some embodiments, R³ is -thiophen-3-yl(R⁶)_(q), q is 1, and R⁶ is—C(═O)R¹⁷.

In some embodiments, R³ is -thiophen-3-yl(R⁶)_(q), q is 1, R⁶ is—C(═O)R¹⁷, and R¹⁷ is —(C₁₋₄ alkyl).

In some embodiments, R³ is -thiophen-3-yl(R⁶)_(q), q is 1, R⁶ is—C(═O)R¹⁷, and R¹⁷ is —(C₁₋₂ alkyl).

In some embodiments, R³ is -thiophen-3-yl(R⁶)_(q), q is 1, R⁶ is—C(═O)R¹⁷, and R¹⁷ is methyl.

In some embodiments, R³ is selected from the group consisting of:

In some embodiments, R³ is -phenyl(R⁸)_(k).

In some embodiments, R³ is -phenyl(R⁸)_(k) and k is 0.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 1 or 2, and each R⁸ isindependently a halide.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 1 or 2, and R⁸ is F.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 1, and R⁸ is F.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is a halideand the other R⁸ is —(C₁₋₆ alkylene)_(p)NHSO₂R¹⁷.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is a halideand the other R⁸ is —(C₁₋₄ alkylene)_(p)NHSO₂R¹⁷, and p is 1.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is a halideand the other R⁸ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁷, and p is 1.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is a halideand the other R⁸ is —CH₂NHSO₂R¹⁷.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is a halideand the other R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is —(C₁₋₄ alkyl).

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is a halideand the other R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is —(C₁₋₂ alkyl).

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is a halideand the other R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is methyl.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is F and theother R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is —(C₁₋₂ alkyl).

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is F and theother R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is methyl.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NR¹³(C₁₋₆ alkylene)NR¹³R¹⁴.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NR¹³(C₁₋₅ alkylene)NR¹³R¹⁴.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NR¹³(C₁₋₄ alkylene)NR¹³R¹⁴.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NR¹³(C₁₋₃ alkylene)NR¹³R¹⁴.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NR¹³CH₂CH₂NR¹³R¹⁴.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, R⁸ is halide and theother R⁸ is —NHCH₂CH₂NR¹³R¹⁴, and R¹³ and R¹⁴ are independently selectedfrom —(C₁₋₆ alkyl).

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NHCH₂CH₂NR¹³R¹⁴, and R¹³ and R¹⁴ are independentlyselected from —(C₁₋₄ alkyl).

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NHCH₂CH₂NR¹³R¹⁴, and R¹³ and R¹⁴ are independentlyselected from —(C₁₋₂ alkyl).

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NHCH₂CH₂NR¹³R¹⁴, and R¹³ and R¹⁴ are both methyl.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is F and theother R⁸ is —NHCH₂CH₂NR¹³R¹⁴, and R¹³ and R¹⁴ are independently selectedfrom —(C₁₋₂ alkyl).

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is F and theother R⁸ is —NHCH₂CH₂NR¹³R¹⁴, and R¹³ and R¹⁴ are both methyl.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —OCH₂CH₂NR²³R²⁴.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —OCH₂CH₂NR²³R²⁴, and R²³ and R²⁴ are independently a—(C₁₋₂ alkyl).

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —OCH₂CH₂NR²³R²⁴, and R²³ and R²⁴ are both methyl.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is F and theother R⁸ is —OCH₂CH₂NR²³R²⁴, and R²³ and R²⁴ are both methyl.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is —(C₁₋₄ alkyl).

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is —(C₁₋₂ alkyl).

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is methyl.

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is F and theother R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is —(C₁₋₂ alkyl).

In some embodiments, R³ is -phenyl(R⁸)_(k), k is 2, one R⁸ is F and theother R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is methyl.

In some embodiments, R³ is selected from the group consisting of:

In some embodiments, R³ is -piperidinyl(R⁷)_(h).

In some embodiments, R³ is -piperidin-1-yl(R⁷)_(h).

In some embodiments, R³ is -piperidin-1-yl(R⁷)_(h) and h is 0.

In some embodiments, R³ is -piperidin-1-yl(R⁷)_(h), h is 1 or 2, andeach R⁷ is independently selected from a halide.

In some embodiments, R³ is -piperazinyl(R⁷)_(h).

In some embodiments, R³ is -piperazin-1-yl(R⁷)_(h).

In some embodiments, R³ is -piperazin-1-yl(R⁷)_(h), h is 1, and R⁷ isC₁₋₃ alkyl.

In some embodiments, R³ is -piperazin-1-yl(R⁷)_(h), h is 1, and R⁷ ismethyl.

In some embodiments, R³ is -morpholinyl(R⁷)_(h).

In some embodiments, R³ is -morpholin-1-yl(R⁷)_(h).

In some embodiments, R³ is -morpholin-1-yl(R⁷)_(h) and h is 0.

In some embodiments, R³ is selected from the group consisting of:

In some embodiments, q is 0.

In some embodiments, at least one R⁴ is a halide.

In some embodiments, at least one R⁴ is a F.

In some embodiments, R⁴ is F.

In some embodiments, at least one R⁴ is —(C₁₋₆ alkyl).

In some embodiments, at least one R⁴ is —(C₁₋₅ alkyl).

In some embodiments, at least one R⁴ is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁴ is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁴ is —(C₁₋₂ alkyl).

In some embodiments, R⁴ is a methyl.

In some embodiments, at least one R⁴ is —(C₁₋₄alkylene)_(p)heterocyclyl(R⁹)_(h) and p is 0 or 1.

In some embodiments, at least one R⁴ is —(C₁₋₃alkylene)_(p)heterocyclyl(R⁹)_(h) and p is 0 or 1.

In some embodiments, at least one R⁴ is —(C₁₋₂alkylene)_(p)heterocyclyl(R⁹)_(h) and p is 0 or 1.

In some embodiments, at least one R⁴ is —CH₂pyrrolidinyl(R⁹)_(h).

In some embodiments, at least one R⁴ is —CH₂pyrrolidinyl(R⁹)_(h) and his 0.

In some embodiments, R⁴ is a —CH₂pyrrolidinyl(R⁹)_(h) and h is 0.

In some embodiments, at least one R⁴ is —CH₂pyrrolidinyl(R⁹)_(h), h is 1or 2, and at least one R⁹ is halide.

In some embodiments, at least one R⁴ is —CH₂pyrrolidinyl(R⁹)_(h), h is 1or 2, and at least one R⁹ is F.

In some embodiments, R⁴ is a —CH₂pyrrolidinyl(R⁹)_(h), h is 1 or 2, andat least one R⁹ is halide.

In some embodiments, R⁴ is —CH₂pyrrolidinyl(R⁹)_(h), h is 1 or 2, and atleast one R⁹ is F.

In some embodiments, R⁴ is a —CH₂pyrrolidinyl(R⁹)_(h), h is 1 or 2, andeach R⁹ is F.

In some embodiments, at least one R⁴ is —CH₂piperidinyl(R⁹)_(h).

In some embodiments, at least one R⁴ is —CH₂piperidinyl(R⁹)_(h) and h is0.

In some embodiments, R⁴ is a —CH₂piperidinyl(R⁹)_(h) and h is 0.

In some embodiments, at least one R⁴ is —CH₂piperidinyl(R⁹)_(h) and atleast one R⁹ is halide.

In some embodiments, at least one R⁴ is —CH₂piperidinyl(R⁹)_(h) and atleast one R⁹ is F.

In some embodiments, at least one R⁴ is —CH₂piperidinyl(R⁹)_(h), h is 1or 2, and at least one R⁹ is halide.

In some embodiments, at least one R⁴ is —CH₂piperidinyl(R⁹)_(h), h is 1or 2, and at least one R⁹ is F.

In some embodiments, R⁴ is —CH₂piperidinyl(R⁹)_(h), h is 1 or 2, andeach R⁹ is a halide.

In some embodiments, R⁴ is —CH₂piperidinyl(R⁹)_(h), h is 1 or 2, andeach R⁹ is F.

In some embodiments, R⁴ is a —CH₂piperidinyl(R⁹)_(h), h is 1 or 2, andeach R⁹ is F.

In some embodiments, R⁴ is a

In some embodiments, at least one R⁴ is —(C₁₋₄alkylene)_(p)carbocyclyl(R¹⁰)_(j).

In some embodiments, at least one R⁴ is —(C₁₋₄alkylene)_(p)carbocyclyl(R¹⁰)_(j) and j is 0 or 1.

In some embodiments, at least one R⁴ is —(C₁₋₃alkylene)_(p)carbocyclyl(R¹⁰)_(j) and j is 0 or 1.

In some embodiments, at least one R⁴ is —(C₁₋₂alkylene)_(p)carbocyclyl(R¹⁰)_(j) and j is 0 or 1.

In some embodiments, at least one R⁴ is —CH₂carbocyclyl(R¹⁰)_(j).

In some embodiments, R⁴ is a —CH₂carbocyclyl(R¹⁰)_(j).

In some embodiments, at least one R⁴ is —(C₁₋₄alkylene)_(p)aryl(R¹¹)_(k) and k is 0 or 1.

In some embodiments, at least one R⁴ is —(C₁₋₃alkylene)_(p)aryl(R¹¹)_(k) and k is 0 or 1.

In some embodiments, at least one R⁴ is —(C₁₋₂alkylene)_(p)aryl(R¹¹)_(k) and k is 0 or 1.

In some embodiments, at least one R⁴ is —CH₂aryl(R¹¹)_(k).

In some embodiments, at least one R⁴ is —CH₂phenyl(R¹¹)_(k).

In some embodiments, R⁴ is a —CH₂phenyl(R¹¹)_(k).

In some embodiments, at least one R⁴ is —NHC(═O)R¹².

In some embodiments, R⁴ is a —NHC(═O)R¹².

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₉alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₈alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₇alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₆alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₅alkyl).

In some embodiments, R⁴ is a —NHC(═O)R¹² and R¹² is —(C₁₋₅ alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₄alkyl).

In some embodiments, R⁴ is a —NHC(═O)R¹² and R¹² is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₃alkyl).

In some embodiments, R⁴ is a —NHC(═O)R¹² and R¹² is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₂alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₂₋₅alkyl).

In some embodiments, R⁴ is a —NHC(═O)R¹² and R¹² is —(C₂₋₅ alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₃₋₄alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is-aryl(R¹⁹)_(k).

In some embodiments, at least one R⁴ is —NHC(═O)R¹², R¹² is-phenyl(R¹⁹)_(k), and k is 0.

In some embodiments, R⁴ is a —NHC(═O)R¹², R¹² is phenyl(R¹⁹)_(k), and kis 0.

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is—CH₂aryl(R¹⁹)_(k).

In some embodiments, at least one R⁴ is —NHC(═O)R¹², R¹² is—CH₂phenyl(R¹⁹)_(k), and k is 0.

In some embodiments, R⁴ is —NHC(═O)R¹², R¹² is —CH₂phenyl(R¹⁹)_(k), andk is 0.

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is-heteroaryl(R¹⁸)_(q).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is-carbocyclyl(R²⁰)_(j).

In some embodiments, at least one R⁴ is —NHC(═O)R¹², R¹² is-carbocyclyl(R²⁰)_(j), and j is 0.

In some embodiments, at least one R⁴ is —NHC(═O)R¹², R¹² is-cyclopropyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHC(═O)R¹², R¹² is -cyclopropyl(R²⁰)_(j),and j is 0.

In some embodiments, at least one R⁴ is —NHC(═O)R¹², R¹² is-cyclobutyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHC(═O)R¹², R¹² is -cyclobutyl(R²⁰)_(j),and j is 0.

In some embodiments, at least one R⁴ is —NHC(═O)R¹², R¹² is-cyclopentyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHC(═O)R¹², R¹² is cyclopentyl(R²⁰)_(j),and j is 0.

In some embodiments, at least one R⁴ is —NHC(═O)R¹², R¹² is-cyclohexyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHC(═O)R¹², R¹² is -cyclohexyl(R²⁰)_(j),and j is 0.

In some embodiments, at least one R⁴ is —NHC(═O)R¹², R¹² is—CH₂carbocyclyl(R²⁰)_(j), and j is 0.

In some embodiments, at least one R⁴ is —NHC(═O)R¹², R¹² is—CH₂cyclopropyl(R²⁰)_(j), and j is 0.

In some embodiments, at least one R⁴ is —NR¹³R¹⁴.

In some embodiments, at least one R⁴ is —NR¹³R¹⁴, and R¹³ and R¹⁴ areindependently selected from the group consisting of H and —(C₁₋₆ alkyl).

In some embodiments, at least one R⁴ is —NR¹³R¹⁴, and R¹³ and R¹⁴ areindependently selected from the group consisting of H and —(C₁₋₅ alkyl).

In some embodiments, at least one R⁴ is —NR¹³R¹⁴, and R¹³ and R¹⁴ areindependently selected from the group consisting of H and —(C₁₋₄ alkyl).

In some embodiments, at least one R⁴ is —NR¹³R¹⁴, and R¹³ and R¹⁴ areindependently selected from the group consisting of H and —(C₁₋₃ alkyl).

In some embodiments, at least one R⁴ is —NR¹³R¹⁴, and R¹³ and R¹⁴ areindependently selected from the group consisting of H and —(C₁₋₂ alkyl).

In some embodiments, at least one R⁴ is —NR¹³R¹⁴, and R¹³ and R¹⁴ areindependently selected from the group consisting of H and methyl.

In some embodiments, at least one R⁴ is —NH₂.

In some embodiments, R⁴ is a —NH₂.

In some embodiments, at least one R⁴ is —NHR¹⁴ and R¹⁴ is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁴ is —NHR¹⁴ and R¹⁴ is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁴ is —NHR¹⁴ and R¹⁴ is —(C₁₋₂ alkyl).

In some embodiments, R⁴ is a —NHR¹⁴ and R¹⁴ is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁴ is —NHR¹⁴ and R¹⁴ is—CH₂aryl(R¹⁹)_(k).

In some embodiments, at least one R⁴ is —NHR¹⁴, R¹⁴ is—CH₂phenyl(R¹⁹)_(k), and k is 0.

In some embodiments, R⁴ is —NHR¹⁴, R¹⁴ is —CH₂phenyl(R¹⁹)_(k), and k is0.

In some embodiments, at least one R⁴ is —NHR¹⁴ and R¹⁴ is—CH₂carbocyclyl(R²⁰)_(j).

In some embodiments, at least one R⁴ is —NHR¹⁴, R¹⁴ is—CH₂cyclopropyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHR¹⁴, R¹⁴ is —CH₂cyclopropyl(R²⁰)_(j),and j is 0.

In some embodiments, at least one R⁴ is —NHR¹⁴, R¹⁴ is—CH₂cyclobutyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHR¹⁴, R¹⁴ is —CH₂cyclobutyl(R²⁰)_(j), andj is 0.

In some embodiments, at least one R⁴ is —NHR¹⁴, R¹⁴ is—CH₂cyclopentyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHR¹⁴, R¹⁴ is —CH₂cyclopentyl(R²⁰)_(j),and j is 0.

In some embodiments, at least one R⁴ is —NHR¹⁴, R¹⁴ is—CH₂cyclohexyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHR¹⁴, R¹⁴ is —CH₂cyclohexyl(R²⁰)_(j), andj is 0.

In some embodiments, at least one R⁴ is —(C₁₋₆ alkylene)NR¹⁵R¹⁶.

In some embodiments, at least one R⁴ is —(C₁₋₅ alkylene)NR¹⁵R¹⁶.

In some embodiments, at least one R⁴ is —(C₁₋₄ alkylene)NR¹⁵R¹⁶.

In some embodiments, at least one R⁴ is —(C₁₋₃ alkylene)NR¹⁵R¹⁶.

In some embodiments, at least one R⁴ is —(C₁₋₂ alkylene)NR¹⁵R¹⁶.

In some embodiments, at least one R⁴ is —CH₂NR¹⁵R¹⁶.

In some embodiments, R⁴ is a —CH₂NR¹⁵R¹⁶.

In some embodiments, at least one R⁴ is —CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₆ alkyl).

In some embodiments, at least one R⁴ is —CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₅ alkyl).

In some embodiments, at least one R⁴ is —CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₄ alkyl).

In some embodiments, at least one R⁴ is —CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₃ alkyl).

In some embodiments, at least one R⁴ is —CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₂ alkyl).

In some embodiments, at least one R⁴ is —CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and methyl.

In some embodiments, R⁴ is a —CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and methyl.

In some embodiments, at least one R⁴ is —CH₂NH₂.

In some embodiments, R⁴ is a —CH₂NH₂.

In some embodiments, at least one R⁴ is —CH₂NMe₂.

In some embodiments, R⁴ is —CH₂NMe₂.

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶ and R¹⁶ is —(C₁₋₄alkyl).

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶ and R¹⁶ is —(C₁₋₃alkyl).

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶ and R¹⁶ is —(C₁₋₂alkyl).

In some embodiments, R⁴ is a —CH₂NHR¹⁶ and R¹⁶ is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶ and R¹⁶ is—CH₂aryl(R¹⁹)_(k).

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶, R¹⁶ is—CH₂phenyl(R¹⁹)_(k), and k is 0.

In some embodiments, R⁴ is a —CH₂NHR¹⁶, R¹⁶ is —CH₂phenyl(R¹⁹)_(k), andk is 0.

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶ and R¹⁶ is—CH₂carbocyclyl(R²⁰)_(j).

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶, R¹⁶ is—CH₂cyclopropyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —CH₂NHR¹⁶, R¹⁶ is —CH₂cyclopropyl(R²⁰)_(j),and j is 0.

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶, R¹⁶ is—CH₂cyclobutyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —CH₂NHR¹⁶, R¹⁶ is —CH₂cyclobutyl(R²⁰)_(j),and j is 0.

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶, R¹⁶ is—CH₂cyclopentyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —CH₂NHR¹⁶, R¹⁶ is —CH₂cyclopentyl(R²⁰)_(j),and j is 0.

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶, R¹⁶ is—CH₂cyclohexyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —CH₂NHR¹⁶, R¹⁶ is —CH₂cyclohexyl(R²⁰)_(j),and j is 0.

In some embodiments, at least one R⁴ is —OR²².

In some embodiments, at least one R⁴ is —OH.

In some embodiments, R⁴ is a —OH.

In some embodiments, at least one R⁴ is —OR²² and R²² is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁴ is —OR²² and R²² is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁴ is —OMe.

In some embodiments, R⁴ is a —OMe.

In some embodiments, at least one R⁴ is —OR²², R²² is-heterocyclyl(R²¹)_(h), and h is 0.

In some embodiments, R⁴ is a —OR²², R²² is heterocyclyl(R²¹)_(h), and his 0.

In some embodiments, at least one R⁴ is —OR²², R²² iscarbocyclyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —OR²², R²² is -carbocyclyl(R²⁰)_(j), and jis 0.

In some embodiments, at least one R⁴ is a —OR²², R²² is —(C₁₋₄alkylene)heterocyclyl(R²¹)_(h), and h is 0.

In some embodiments, at least one R⁴ is —OR²², R²² is—(CH₂CH₂)heterocyclyl(R²¹)_(h), and h is 0.

In some embodiments, R⁴ is a —OR²², R²² is—(CH₂CH₂)heterocyclyl(R²¹)_(h), and h is 0.

In some embodiments, at least one R⁴ is —OR²², R²² is —(C₁₋₄alkylene)NR²³R²⁴ and R²³ and R²⁴ are independently a —(C₁₋₄ alkyl).

In some embodiments, at least one R⁴ is —OR²², R²² is —(CH₂CH₂)NR²³R²⁴and R²³ and R²⁴ are independently a —(C₁₋₂ alkyl).

In some embodiments, at least one R⁴ is —OR²², and R²² is —(CH₂CH₂)NMe₂.

In some embodiments, R⁴ is a —OR²², and R²² is —(CH₂CH₂)NMe₂.

In some embodiments, at least one R⁴ is —OR²², R²² is —C₁₋₄alkylene)aryl(R¹⁹)_(k), k is 0 or 1 and R¹⁹ is halide.

In some embodiments, at least one R⁴ is —OR²², R²² is—(CH₂CH₂)phenyl(R¹⁹)_(k), k is 0 or 1 and R¹⁹ is a halide.

In some embodiments, R⁴ is a —OR²², R²² is —(CH₂CH₂)phenyl(R¹⁹)_(k), kis 0 or 1 and R¹⁹ is a halide.

In some embodiments, at least one R⁴ is —OR²², R²² is—(CH₂)phenyl(R¹⁹)_(k), k is 0 or 1 and R¹⁹ is a halide.

In some embodiments, R⁴ is a —OR²², R²² is —(CH₂)phenyl(R¹⁹)_(k), k is 0or 1 and R¹⁹ is a halide.

In some embodiments, h is 0.

In some embodiments, at least one R⁵ is a halide.

In some embodiments, at least one R⁵ is a F.

In some embodiments, at least one R⁵ is —(C₁₋₆ alkyl).

In some embodiments, at least one R⁵ is —(C₁₋₅ alkyl).

In some embodiments, at least one R⁵ is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁵ is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁵ is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁵ is methyl.

In some embodiments, at least one R⁶ is a halide.

In some embodiments, at least one R⁶ is a F.

In some embodiments, at least one R⁶ is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁶ is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁶ is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁶ is methyl.

In some embodiments, R⁶ is a methyl.

In some embodiments, at least one R⁶ is —C(═O)(C₁₋₃ alkyl).

In some embodiments, at least one R⁶ is —C(═O)Me.

In some embodiments, R⁶ is a C(═O)Me.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is -phenyl(R⁸)_(k); k is 1 or 2;and R⁸ is F.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is -phenyl(R⁸)_(k); k is 2; one R⁸is F and the other R⁸ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁷; p is 1; and R¹⁷is —(C₁₋₃ alkyl).

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is -phenyl(R⁸)_(k); k is 2; one R⁸is F and the other R⁸ is —NH(C₁₋₆ alkylene)NR¹³R¹⁴; and R¹³ and R¹⁴ areindependently selected from —(C₁₋₃ alkyl).

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is —NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is -heteroaryl(R⁶)_(q),wherein q is 1; R⁶ is selected from the group consisting of halide,—(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃ alkyl); and the heteroarylis selected from the group consisting of pyridine, furan, thiophene, andimidazole.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is -heterocyclyl(R⁷)_(h); h is 1or 2; and R⁷ is selected from the group consisting of halide and —(C₁₋₂alkyl).

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is -carbocyclyl(R²⁰)_(j); j is 0; R³ is-phenyl(R⁸)_(k); k is 1 or 2; R⁸ is F; and the carbocyclyl is selectedfrom the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is -carbocyclyl(R²⁰)_(j); j is 0; R³ is-phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is —(C₁₋₂alkylene)_(p)NHSO₂R¹⁷; p is 1; R¹⁷ is —(C₁₋₃ alkyl); and the carbocyclylis selected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is -carbocyclyl(R²⁰)_(j); j is 0; R³ is-phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is —NH(C₁₋₆alkylene)NR¹³R¹⁴; R¹³ and R¹⁴ are independently selected from —(C₁₋₃alkyl); and the carbocyclyl is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is —NHC(═O)R¹²; R¹² is -carbocyclyl(R²⁰)_(j); j is 0; R³ is-heteroaryl(R⁶)_(q), wherein q is 1; R⁶ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —C₁₋₃ alkyl;the heteroaryl is selected from the group consisting of pyridine, furan,thiophene, and imidazole; and the carbocyclyl is selected from the groupconsisting of cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is -carbocyclyl(R²⁰)_(j); j is 0; R³ is-heterocyclyl(R⁷)_(h); h is 1 or 2; R⁷ is selected from the groupconsisting of halide and —(C₁₋₂ alkyl); and the carbocyclyl is selectedfrom the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶; R¹³ andR¹⁵ are independently selected from the group consisting of H and —(C₁₋₃alkyl); R¹⁴ and R¹⁶ are independently selected from the group consistingof H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j),wherein k and j are 0; R³ is -phenyl(R⁸)_(k), wherein k is 1 or 2; R⁸ isF; and the carbocyclyl is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶; R¹³ andR¹⁵ are independently selected from the group consisting of H and —(C₁₋₃alkyl); R¹⁴ and R¹⁶ are independently selected from the group consistingof H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j),wherein k and j are 0; R³ is -phenyl(R⁸)_(k), wherein k is 2; one R⁸ isF and the other R⁸ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁷; p is 1; R¹⁷ is—(C₁₋₃ alkyl); and the carbocyclyl is selected from the group consistingof cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶, whereinR¹³ and R¹⁵ are independently selected from the group consisting of Hand —(C₁₋₃ alkyl), and R¹⁴ and R¹⁶ are independently selected from thegroup consisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j), wherein k and j are 0; R³ is -phenyl(R⁸)_(k),wherein k is 2; one R⁸ is F and the other R⁸ is —NH(C₁₋₆alkylene)NR¹³R¹⁴, wherein R¹³ and R¹⁴ are independently selected from—(C₁₋₃ alkyl); and the carbocyclyl is selected from the group consistingof cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is selected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶;R¹³ and R¹⁵ are independently selected from the group consisting of Hand —(C₁₋₃ alkyl); R¹⁴ and R¹⁶ are independently selected from the groupconsisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j), wherein k and j are 0; R³ is-heteroaryl(R⁶)_(q), wherein q is 1; R⁶ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃alkyl); the heteroaryl is selected from the group consisting ofpyridine, furan, thiophene, and imidazole; and the carbocyclyl isselected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶; R¹³ andR¹⁵ are independently selected from the group consisting of H and —(C₁₋₃alkyl); R¹⁴ and R¹⁶ are independently selected from the group consistingof H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j),wherein k and j are 0; R³ is -heterocyclyl(R⁷)_(h); h is 1 or 2; R⁷ isselected from the group consisting of halide and —(C₁₋₂ alkyl); and thecarbocyclyl is selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is -phenyl(R⁸)_(k); k is1 or 2; R⁸ is F; and the heterocyclyl is selected from the groupconsisting of pyrrolidine and piperidine.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is -phenyl(R⁸)_(k); k is2; one R⁸ is F and the other R⁸ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁷; p is 1;R¹⁷ is —(C₁₋₃ alkyl); and the heterocyclyl is selected from the groupconsisting of pyrrolidine and piperidine.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is -phenyl(R⁸)_(k); k is2; and R⁸ is one F and the other R⁸ —NH(C₁₋₆ alkylene)NR¹³R¹⁴; R¹³ andR¹⁴ are independently selected from —(C₁₋₃ alkyl); and the heterocyclylis selected from the group consisting of pyrrolidine and piperidine.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is —CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is-heteroaryl(R⁶)_(q), wherein q is 1; R⁶ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃alkyl); the heteroaryl is selected from the group consisting ofpyridine, furan, thiophene, and imidazole; and the heterocyclyl isselected from the group consisting of pyrrolidine and piperidine.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h), wherein h is 0-2; R⁹ is F; R³ is-heterocyclyl(R⁷)_(h), wherein h is 1 or 2; R⁷ is selected from thegroup consisting of halide and —(C₁₋₂ alkyl); and the heterocyclyl isselected from the group consisting of pyrrolidine and piperidine.

In some embodiments, R² is H; R¹ is -pyrimidinyl(R⁴)_(q); q is 0; R³ is-phenyl(R⁸)_(k); k is 1 or 2; and R⁸ is F.

In some embodiments, R² is H; R¹ is -pyrimidinyl(R⁴)_(q); q is 0; R³ is-phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is —(C₁₋₂alkylene)_(p)NHSO₂R¹⁷; p is 1; and R¹⁷ is —(C₁₋₃ alkyl).

In some embodiments, R² is H; R¹ is -pyrimidinyl(R⁴)_(q); q is 0; R³ is-phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is —NH(C₁₋₆alkylene)NR¹³R¹⁴; and R¹³ and R¹⁴ are independently selected from —(C₁₋₃alkyl).

In some embodiments, R² is H; R¹ is -pyrimidinyl(R⁴)_(q), wherein q is0; R³ is heteroaryl(R⁶)_(q), wherein q is 1; R⁶ is selected from thegroup consisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃alkyl); and the heteroaryl is selected from the group consisting ofpyridine, furan, thiophene, and imidazole.

In some embodiments, R² is H; R¹ is -pyrimidinyl(R⁴)_(q); q is 0; R³ isheterocyclyl(R⁷)_(h); h is 1 or 2; R⁷ is selected from the groupconsisting of halide and —(C₁₋₂ alkyl).

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is -phenyl(R⁸)_(k); k is 1 or 2;and R⁸ is F.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is -phenyl(R⁸)_(k); k is 2; one R⁸is F and the other R⁸ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁷; p is 1; and R¹⁷is —(C₁₋₃ alkyl).

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is -phenyl(R⁸)_(k); k is 2; one R⁸is F and the other R⁸ is —NH(C₁₋₆ alkylene)NR¹³R¹⁴; and R¹³ and R¹⁴ areindependently selected from —(C₁₋₃ alkyl).

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is —NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is -heteroaryl(R⁶)_(q),wherein q is 1; R⁶ is selected from the group consisting of halide,—(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃ alkyl); and the heteroarylis selected from the group consisting of pyridine, furan, thiophene, andimidazole.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is -heterocyclyl(R⁷)_(h); h is 1or 2; and R⁷ is selected from the group consisting of halide and —(C₁₋₂alkyl).

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is -carbocyclyl(R²⁰)_(j); j is 0; R³ is-phenyl(R⁸)_(k); k is 1 or 2; R⁸ is F; and the carbocyclyl is selectedfrom the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is -carbocyclyl(R²⁰)_(j); j is 0; R³ is-phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is —(C₁₋₂alkylene)_(p)NHSO₂R¹⁷; p is 1; R¹⁷ is —(C₁₋₃ alkyl); and the carbocyclylis selected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is -carbocyclyl(R²⁰)_(j); j is 0; R³ is-phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is —NH(C₁₋₆alkylene)NR¹³R¹⁴; R¹³ and R¹⁴ are independently selected from —(C₁₋₃alkyl); and the carbocyclyl is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is —NHC(═O)R¹²; R¹² is -carbocyclyl(R²⁰)_(j); j is 0; R³ is-heteroaryl(R⁶)_(q), wherein q is 1; R⁶ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —C₁₋₃ alkyl;the heteroaryl is selected from the group consisting of pyridine, furan,thiophene, and imidazole; and the carbocyclyl is selected from the groupconsisting of cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴); q is 1; R⁴ isNHC(═O)R¹²; R¹² is -carbocyclyl(R²⁰)_(j); j is 0; R³ is-heterocyclyl(R⁷)_(h); h is 1 or 2; R⁷ is selected from the groupconsisting of halide and —(C₁₋₂ alkyl); and the carbocyclyl is selectedfrom the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶; R¹³ andR¹⁵ are independently selected from the group consisting of H and —(C₁₋₃alkyl); R¹⁴ and R¹⁶ are independently selected from the group consistingof H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j),wherein k and j are 0; R³ is -phenyl(R⁸)_(k), wherein k is 1 or 2; R⁸ isF; and the carbocyclyl is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶; R¹³ andR¹⁵ are independently selected from the group consisting of H and —(C₁₋₃alkyl); R¹⁴ and R¹⁶ are independently selected from the group consistingof H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j),wherein k and j are 0; R³ is -phenyl(R⁸)_(k) wherein k is 2; one R⁸ is Fand the other R⁸ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁷; p is 1; R¹⁷ is —(C₁₋₃alkyl); and the carbocyclyl is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶, whereinR¹³ and R¹⁵ are independently selected from the group consisting of Hand —(C₁₋₃ alkyl), and R¹⁴ and R¹⁶ are independently selected from thegroup consisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j), wherein k and j are 0; R³ is -phenyl(R⁸)_(k),wherein k is 2; one R⁸ is F and the other R⁸ is —NH(C₁₋₆alkylene)NR¹³R¹⁴, wherein R¹³ and R¹⁴ are independently selected from—(C₁₋₃ alkyl); and the carbocyclyl is selected from the group consistingof cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is selected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶;R¹³ and R¹⁵ are independently selected from the group consisting of Hand —(C₁₋₃ alkyl); R¹⁴ and R¹⁶ are independently selected from the groupconsisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j), wherein k and j are 0; R³ is-heteroaryl(R⁶)_(q), wherein q is 1; R⁶ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃alkyl); the heteroaryl is selected from the group consisting ofpyridine, furan, thiophene, and imidazole; and the carbocyclyl isselected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶; R¹³ andR¹⁵ are independently selected from the group consisting of H and —(C₁₋₃alkyl); R¹⁴ and R¹⁶ are independently selected from the group consistingof H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j),wherein k and j are 0; R³ is -heterocyclyl(R⁷)_(h); h is 1 or 2; R⁷ isselected from the group consisting of halide and —(C₁₋₂ alkyl); and thecarbocyclyl is selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is -phenyl(R⁸)_(k); k is1 or 2; R⁸ is F; and the heterocyclyl is selected from the groupconsisting of pyrrolidine and piperidine.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is -phenyl(R⁸)_(k); k is2; one R⁸ is F and the other R⁸ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁷; p is 1;R¹⁷ is —(C₁₋₃ alkyl); and the heterocyclyl is selected from the groupconsisting of pyrrolidine and piperidine.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is -phenyl(R⁸)_(k); k is2; and R⁸ is one F and the other R⁸ is —NH(C₁₋₆ alkylene)NR¹³R¹⁴; R¹³and R¹⁴ are independently selected from —(C₁₋₃ alkyl); and theheterocyclyl is selected from the group consisting of pyrrolidine andpiperidine.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is —CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is-heteroaryl(R⁶)_(q), wherein q is 1; R⁶ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃alkyl); the heteroaryl is selected from the group consisting ofpyridine, furan, thiophene, and imidazole; and the heterocyclyl isselected from the group consisting of pyrrolidine and piperidine.

In some embodiments, R² is F; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h), wherein h is 0-2; R⁹ is F; R³ is-heterocyclyl(R⁷)_(h), wherein h is 1 or 2; R⁷ is selected from thegroup consisting of halide and —(C₁₋₂ alkyl); and the heterocyclyl isselected from the group consisting of pyrrolidine and piperidine.

In some embodiments, R² is F; R¹ is -pyrimidinyl(R⁴)_(q); q is 0; R³ is-phenyl(R⁸)_(k); k is 1 or 2; and R⁸ is F.

In some embodiments, R² is F; R¹ is -pyrimidinyl(R⁴)_(q); q is 0; R³ is-phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is —(C₁₋₂alkylene)_(p)NHSO₂R¹⁷; p is 1; and R¹⁷ is —(C₁₋₃ alkyl).

In some embodiments, R² is F; R¹ is -pyrimidinyl(R⁴)_(q); q is 0; R³ is-phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is —NH(C₁₋₆alkylene)NR¹³R¹⁴; and R¹³ and R¹⁴ are independently selected from —(C₁₋₃alkyl).

In some embodiments, R² is F; R¹ is -pyrimidinyl(R⁴)_(q), wherein q is0; R³ is -heteroaryl(R⁶)_(q), wherein q is 1; R⁶ is selected from thegroup consisting of halide, —(C₁₋₂ alkyl), and C(═O)R¹⁷; R¹⁷ is —(C₁₋₃alkyl); and the heteroaryl is selected from the group consisting ofpyridine, furan, thiophene, and imidazole.

In some embodiments, R² is F; R¹ is -pyrimidinyl(R⁴)_(q); q is 0; R³ is-heterocyclyl(R⁷)_(h); h is 1 or 2; R⁷ is selected from the groupconsisting of halide and —(C₁₋₂ alkyl).

In some embodiments, R² is H; R¹ is -pyrazol-4-yl(R⁴)_(q); q is 0 or 1;R⁴ is —(C₁₋₃ alkyl); R³ is -phenyl(R⁸)_(k); k is 1 or 2; and R⁸ is F.

In some embodiments, R² is H; R¹ is -imidazol-5-yl(R⁴)_(q); q is 1 or 2;each R⁴ is independently selected from —(C₁₋₃ alkyl); R³ is-phenyl(R⁸)_(k); k is 1 or 2; and R⁸ is F.

In some embodiments, R² is H; R¹ is -pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—OR²²; R²² is selected from the group consisting of H and —(C₁₋₃ alkyl);R³ is -phenyl(R⁸)_(k); k is 1 or 2; and R⁸ is F.

Illustrative compounds of Formula (I) are shown in Table 1.

TABLE 1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89

90

91

92

93

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

117

118

119

120

121

122

123

124

125

126

127

128

129

130

131

132

133

134

135

136

137

138

139

140

141

142

143

144

145

146

147

148

149

150

151

152

153

154

155

156

157

158

159

160

161

162

163

164

165

166

167

168

169

170

171

172

173

174

175

176

177

178

179

180

181

182

183

184

185

186

187

188

189

190

191

192

193

194

195

196

197

198

199

200

201

202

203

204

205

206

207

208

209

210

211

212

213

214

215

216

217

218

219

220

221

222

223

224

225

226

227

228

229

230

231

232

233

234

235

236

237

238

239

240

241

242

243

244

245

246

247

248

249

250

251

252

253

254

255

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257

258

259

260

261

262

263

264

265

266

267

268

269

270

271

272

273

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275

276

277

278

279

280

281

282

283

284

285

286

287

288

289

290

291

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297

298

299

300

301

302

303

304

305

306

307

308

309

310

311

312

313

314

315

316

317

318

319

320

321

322

323

324

325

326

327

328

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342

343

344

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400

401

402

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419

420

421

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423

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425

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427

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431

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455

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457

458

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473

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477

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480

481

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485

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494

495

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519

520

521

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523

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531

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539

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541

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569

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719

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726

727

728

729

730

731

732

733

734

735

736

737

738

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745

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764

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766

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769

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771

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784

785

786

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790

791

792

793

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795

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799

800

801

802

803

804

805

806

807

808

809

810

811

812

813

814

815

816

817

818

819

820

821

822

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825

826

827

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829

830

831

832

833

834

835

836

837

838

839

840

841

842

843

844

845

846

847

848

849

850

851

852

853

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855

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865

866

867

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870

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890

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910

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912

913

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920

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930

931

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938

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940

941

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961

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987

988

989

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992

993

994

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999

1000

1001

1002

1003

1004

1005

1006

1007

1008

1009

1010

1011

1012

1013

1014

1015

1016

1017

1018

1019

1020

1021

1022

1023

1024

1025

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1033

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1037

1038

1039

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1081

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1097

1098

1099

1100

1101

1102

1103

1104

1105

1106

1107

1108

1109

1110

1111

1112

1113

1114

1115

1116

1117

1118

1119

1120

1121

1122

1123

1124

1125

1126

1127

1128

1129

1130

1131

1132

1133

1134

1135

1136

1137

1138

1139

1140

1141

1142

1143

1144

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1176

1177

1178

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1186

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1188

1189

1190

1191

1192

1193

1194

1195

1196

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1198

1199

1200

1201

1202

1203

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1234

1235

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1471

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1476

1477Administration and Pharmaceutical Compositions

Some embodiments include pharmaceutical compositions comprising: (a) atherapeutically effective amount of a compound provided herein, or itscorresponding enantiomer, diastereoisomer or tautomer, orpharmaceutically acceptable salt; and (b) a pharmaceutically acceptablecarrier.

The compounds provided herein may also be useful in combination(administered together or sequentially) with other known agents.

Non-limiting examples of diseases which can be treated with acombination of a compound of Formula (I) and other known agents arecolorectal cancer, ovarian cancer, retinitis pigmentosa, maculardegeneration, diabetic retinopathy, idiopathic pulmonaryfibrosis/pulmonary fibrosis, and osteoarthritis.

In some embodiments, colorectal cancer can be treated with a combinationof a compound of Formula (I) and one or more of the following drugs:5-Fluorouracil (5-FU), which can be administered with the vitamin-likedrug leucovorin (also called folinic acid); capecitabine (XELODA®),irinotecan (CAMPOSTAR®), oxaliplatin (ELOXATIN®). Examples ofcombinations of these drugs which could be further combined with acompound of Formula (I) are FOLFOX (5-FU, leucovorin, and oxaliplatin),FOLFIRI (5-FU, leucovorin, and irinotecan), FOLFOXIRI (leucovorin, 5-FU,oxaliplatin, and irinotecan) and CapeOx (Capecitabine and oxaliplatin).For rectal cancer, chemo with 5-FU or capecitabine combined withradiation may be given before surgery (neoadjuvant treatment).

In some embodiments, ovarian cancer can be treated with a combination ofa compound of Formula (I) and one or more of the following drugs:Topotecan, Liposomal doxorubicin (DOXIL®), Gemcitabine (GEMZAR®),Cyclophosphamide (CYTOXAN®), Vinorelbine (NAVELBINE®), Ifosfamide(IFEX®), Etoposide (VP-16), Altretamine (HEXALEN®), Capecitabine(XELODA®), Irinotecan (CPT-11, CAMPTOSAR®), Melphalan, Pemetrexed(ALIMTA®) and Albumin bound paclitaxel (nab-paclitaxel, ABRAXANE®).Examples of combinations of these drugs which could be further combinedwith a compound of Formula (I) are TIP (paclitaxel [Taxol], ifosfamide,and cisplatin), VeIP (vinblastine, ifosfamide, and cisplatin) and VIP(etoposide [VP-16], ifosfamide, and cisplatin).

In some embodiments, a compound of Formula (I) can be used to treatcancer in combination with any of the following methods: (a) Hormonetherapy such as aromatase inhibitors, LHRH [luteinizinghormone-releasing hormone] analogs and inhibitors, and others; (b)Ablation or embolization procedures such as radiofrequency ablation(RFA), ethanol (alcohol) ablation, microwave thermotherapy andcryosurgery (cryotherapy); (c) Chemotherapy using alkylating agents suchas cisplatin and carboplatin, oxaliplatin, mechlorethamine,cyclophosphamide, chlorambucil and ifosfamide; (d) Chemotherapy usinganti-metabolites such as azathioprine and mercaptopurine; (e)Chemotherapy using plant alkaloids and terpenoids such as vincaalkaloids (i.e. Vincristine, Vinblastine, Vinorelbine and Vindesine) andtaxanes; (f) Chemotherapy using podophyllotoxin, etoposide, teniposideand docetaxel; (g) Chemotherapy using topoisomerase inhibitors such asirinotecan, topotecan, amsacrine, etoposide, etoposide phosphate, andteniposide; (h) Chemotherapy using cytotoxic antibiotics such asactinomycin, anthracyclines, doxorubicin, daunorubicin, valrubicin,idarubicin, epirubicin, bleomycin, plicamycin and mitomycin; (i)Chemotherapy using tyrosine-kinase inhibitors such as Imatinib mesylate(GLEEVEC®, also known as STI-571), Gefitinib (Iressa, also known asZD1839), Erlotinib (marketed as TARCEVA®), Bortezomib (VELCADE®),tamoxifen, tofacitinib, crizotinib, Bcl-2 inhibitors (e.g. obatoclax inclinical trials, ABT-263, and Gossypol), PARP inhibitors (e.g. Iniparib,Olaparib in clinical trials), PI3K inhibitors (eg. perifosine in a phaseIII trial), VEGF Receptor 2 inhibitors (e.g. Apatinib), AN-152,(AEZS-108), Braf inhibitors (e.g. vemurafenib, dabrafenib and LGX818),MEK inhibitors (e.g. trametinib and MEK162), CDK inhibitors, (e.g.PD-0332991), salinomycin and Sorafenib; (j) Chemotherapy usingmonoclonal antibodies such as Rituximab (marketed as MABTHERA® orRITUXAN®), Trastuzumab (Herceptin also known as ErbB2), Cetuximab(marketed as ERBITUX®), and Bevacizumab (marketed as AVASTIN®); and (k)radiation therapy.

In some embodiments, diabetic retinopathy can be treated with acombination of a compound of Formula (I) and one or more of thefollowing natural supplements: Bilberry, Butcher's broom, Ginkgo, Grapeseed extract, and Pycnogenol (Pine bark).

In some embodiments, idiopathic pulmonary fibrosis/pulmonary fibrosiscan be treated with a combination of a compound of Formula (I) and oneor more of the following drugs: pirfenidone (pirfenidone was approvedfor use in 2011 in Europe under the brand name Esbriet®), prednisone,azathioprine, N-acetylcysteine, interferon-γ 1b, bosentan (bosentan iscurrently being studied in patients with IPF, [The American Journal ofRespiratory and Critical Care Medicine (2011), 184(1), 92-9]),Nintedanib (BIBF 1120 and Vargatef), QAX576 [British Journal ofPharmacology (2011), 163(1), 141-172], and anti-inflammatory agents suchas corticosteroids.

In some embodiments, a compound of Formula (I) can be used to treatidiopathic pulmonary fibrosis/pulmonary fibrosis in combination with anyof the following methods: oxygen therapy, pulmonary rehabilitation andsurgery.

In some embodiments, a compound of Formula (I) can be used to treatosteoarthritis in combination with any of the following methods: (a)Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen,naproxen, aspirin and acetaminophen; (b) physical therapy; (c)injections of corticosteroid medications; (d) injections of hyaluronicacid derivatives (e.g. Hyalgan, Synvisc); (e) narcotics, like codeine;(f) in combination with braces and/or shoe inserts or any device thatcan immobilize or support your joint to help you keep pressure off it(e.g., splints, braces, shoe inserts or other medical devices); (g)realigning bones (osteotomy); (h) joint replacement (arthroplasty); and(i) in combination with a chronic pain class.

In some embodiments, macular degeneration can be treated with acombination of a compound of Formula (I) and one or more of thefollowing drugs: Bevacizumab (Avastin®), Ranibizumab (Lucentis®),Pegaptanib (Macugen), Aflibercept (Eylea®), verteporfin (Visudyne®) incombination with photodynamic therapy (PDT) or with any of the followingmethods: (a) in combination with laser to destroy abnormal blood vessels(photocoagulation); and (b) in combination with increased vitamin intakeof antioxidant vitamins and zinc.

In some embodiments, retinitis pigmentosa can be treated with acombination of a compound of Formula (I) and one or more of thefollowing drugs: UF-021 (Ocuseva™) vitamin A palmitate and pikachurin orwith any of the following methods: (a) with the Argus® II retinalimplant; and (b) with stem cell and/or gene therapy.

Administration of the compounds disclosed herein or the pharmaceuticallyacceptable salts thereof can be via any of the accepted modes ofadministration, including, but not limited to, orally, subcutaneously,intravenously, intranasally, topically, transdermally,intraperitoneally, intramuscularly, intrapulmonarilly, vaginally,rectally, ontologically, neuro-otologically, intraocularly,subconjuctivally, via anterior eye chamber injection, intravitreally,intraperitoneally, intrathecally, intracystically, intrapleurally, viawound irrigation, intrabuccally, intra-abdominally, intra-articularly,intra-aurally, intrabronchially, intracapsularly, intrameningeally, viainhalation, via endotracheal or endobronchial instillation, via directinstillation into pulmonary cavities, intraspinally, intrasynovially,intrathoracically, via thoracostomy irrigation, epidurally,intratympanically, intracisternally, intravascularly,intraventricularly, intraosseously, via irrigation of infected bone, orvia application as part of any admixture with a prosthetic devices. Insome embodiments, the administration method includes oral or parenteraladministration.

Compounds provided herein intended for pharmaceutical use may beadministered as crystalline or amorphous products. Pharmaceuticallyacceptable compositions may include solid, semi-solid, liquid,solutions, colloidal, liposomes, emulsions, suspensions, complexes,coacervates and aerosols. Dosage forms, such as, e.g., tablets,capsules, powders, liquids, suspensions, suppositories, aerosols,implants, controlled release or the like. They may be obtained, forexample, as solid plugs, powders, or films by methods such asprecipitation, crystallization, milling, grinding, supercritical fluidprocessing, coacervation, complex coacervation, encapsulation,emulsification, complexation, freeze drying, spray drying, orevaporative drying. Microwave or radio frequency drying may be used forthis purpose. The compounds can also be administered in sustained orcontrolled release dosage forms, including depot injections, osmoticpumps, pills (tablets and or capsules), transdermal (includingelectrotransport) patches, implants and the like, for prolonged and/ortimed, pulsed administration at a predetermined rate.

The compounds can be administered either alone or in combination with aconventional pharmaceutical carrier, excipient or the like.Pharmaceutically acceptable excipients include, but are not limited to,ion exchangers, alumina, aluminum stearate, lecithin, self-emulsifyingdrug delivery systems (SEDDS) such as d-α-tocopherol polyethylene glycol1000 succinate, surfactants used in pharmaceutical dosage forms such asTweens, poloxamers or other similar polymeric delivery matrices, serumproteins, such as human serum albumin, buffer substances such asphosphates, tris, glycine, sorbic acid, potassium sorbate, partialglyceride mixtures of saturated vegetable fatty acids, water, salts orelectrolytes, such as protamine sulfate, disodium hydrogen phosphate,potassium hydrogen phosphate, sodium-chloride, zinc salts, colloidalsilica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-basedsubstances, polyethylene glycol, sodium carboxymethyl cellulose,polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, andwool fat. Cyclodextrins such as α-, β, and γ-cyclodextrin, or chemicallymodified derivatives such as hydroxyalkylcyclodextrins, including 2- and3-hydroxypropyl-β-cyclodextrins, or other solubilized derivatives canalso be used to enhance delivery of compounds described herein. Dosageforms or compositions containing a compound as described herein in therange of 0.005% to 100% with the balance made up from non-toxic carriermay be prepared. The contemplated compositions may contain 0.001%-100%of a compound provided herein, in one embodiment 0.1-95%, in anotherembodiment 75-85%, in a further embodiment 20-80%. Actual methods ofpreparing such dosage forms are known, or will be apparent, to thoseskilled in this art; for example, see Remington: The Science andPractice of Pharmacy, 22^(nd) Edition (Pharmaceutical Press, London, UK.2012).

In one embodiment, the compositions will take the form of a unit dosageform such as a pill or tablet and thus the composition may contain,along with a compound provided herein, a diluent such as lactose,sucrose, dicalcium phosphate, or the like; a lubricant such as magnesiumstearate or the like; and a binder such as starch, gum acacia,polyvinylpyrrolidine, gelatin, cellulose, cellulose derivatives or thelike. In another solid dosage form, a powder, marume, solution orsuspension (e.g., in propylene carbonate, vegetable oils, PEG's,poloxamer 124 or triglycerides) is encapsulated in a capsule (gelatin orcellulose base capsule). Unit dosage forms in which one or morecompounds provided herein or additional active agents are physicallyseparated are also contemplated; e.g., capsules with granules (ortablets in a capsule) of each drug; two-layer tablets; two-compartmentgel caps, etc. Enteric coated or delayed release oral dosage forms arealso contemplated.

Liquid pharmaceutically administrable compositions can, for example, beprepared by dissolving, dispersing, etc. a compound provided herein andoptional pharmaceutical adjuvants in a carrier (e.g., water, saline,aqueous dextrose, glycerol, glycols, ethanol or the like) to form asolution, colloid, liposome, emulsion, complexes, coacervate orsuspension. If desired, the pharmaceutical composition can also containminor amounts of nontoxic auxiliary substances such as wetting agents,emulsifying agents, co-solvents, solubilizing agents, pH bufferingagents and the like (e.g., sodium acetate, sodium citrate, cyclodextrinderivatives, sorbitan monolaurate, triethanolamine acetate,triethanolamine oleate, and the like).

In some embodiments, the unit dosage of compounds of Formula (I) isabout 0.25 mg/Kg to about 50 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 0.25 mg/Kg to about 20 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 0.50 mg/Kg to about 19 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 0.75 mg/Kg to about 18 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 1.0 mg/Kg to about 17 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 1.25 mg/Kg to about 16 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 1.50 mg/Kg to about 15 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 1.75 mg/Kg to about 14 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 2.0 mg/Kg to about 13 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 3.0 mg/Kg to about 12 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 4.0 mg/Kg to about 11 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 5.0 mg/Kg to about 10 mg/Kg in humans.

In some embodiments, the compositions are provided in unit dosage formssuitable for single administration.

In some embodiments, the compositions are provided in unit dosage formssuitable for twice a day administration.

In some embodiments, the compositions are provided in unit dosage formssuitable for three times a day administration.

Injectables can be prepared in conventional forms, either as liquidsolutions, colloid, liposomes, complexes, coacervate or suspensions, asemulsions, or in solid forms suitable for reconstitution in liquid priorto injection. The percentage of a compound provided herein contained insuch parenteral compositions is highly dependent on the specific naturethereof, as well as the activity of the compound and the needs of thepatient. However, percentages of active ingredient of 0.01% to 10% insolution are employable, and could be higher if the composition is asolid or suspension, which could be subsequently diluted to the abovepercentages.

In some embodiments, the composition will comprise about 0.1-10% of theactive agent in solution.

In some embodiments, the composition will comprise about 0.1-5% of theactive agent in solution.

In some embodiments, the composition will comprise about 0.1-4% of theactive agent in solution.

In some embodiments, the composition will comprise about 0.15-3% of theactive agent in solution.

In some embodiments, the composition will comprise about 0.2-2% of theactive agent in solution.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-96 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-72 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-48 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-24 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-12 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-6 hours.

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 5 mg/m² to about 300mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 5 mg/m² to about 200mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 5 mg/m² to about 100mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 10 mg/m² to about 50mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 50 mg/m² to about 200mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 75 mg/m² to about 175mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 100 mg/m² to about 150mg/m².

It is to be noted that concentrations and dosage values may also varydepending on the specific compound and the severity of the condition tobe alleviated. It is to be further understood that for any particularpatient, specific dosage regimens should be adjusted over time accordingto the individual need and the professional judgment of the personadministering or supervising the administration of the compositions, andthat the concentration ranges set forth herein are exemplary only andare not intended to limit the scope or practice of the claimedcompositions.

In one embodiment, the compositions can be administered to therespiratory tract (including nasal and pulmonary) e.g., through anebulizer, metered-dose inhalers, atomizer, mister, aerosol, dry powderinhaler, insufflator, liquid instillation or other suitable device ortechnique.

In some embodiments, aerosols intended for delivery to the nasal mucosaare provided for inhalation through the nose. For optimal delivery tothe nasal cavities, inhaled particle sizes of about 5 to about 100microns are useful, with particle sizes of about 10 to about 60 micronsbeing preferred. For nasal delivery, a larger inhaled particle size maybe desired to maximize impaction on the nasal mucosa and to minimize orprevent pulmonary deposition of the administered formulation. In someembodiments, aerosols intended for delivery to the lung are provided forinhalation through the nose or the mouth. For delivery to the lung,inhaled aerodynamic particle sizes of about less than 10 μm are useful(e.g., about 1 to about 10 microns). Inhaled particles may be defined asliquid droplets containing dissolved drug, liquid droplets containingsuspended drug particles (in cases where the drug is insoluble in thesuspending medium), dry particles of pure drug substance, drug substanceincorporated with excipients, liposomes, emulsions, colloidal systems,coacervates, aggregates of drug nanoparticles, or dry particles of adiluent which contain embedded drug nanoparticles.

In some embodiments, compounds of Formula (I) disclosed herein intendedfor respiratory delivery (either systemic or local) can be administeredas aqueous formulations, as non-aqueous solutions or suspensions, assuspensions or solutions in halogenated hydrocarbon propellants with orwithout alcohol, as a colloidal system, as emulsions, coacervates, or asdry powders. Aqueous formulations may be aerosolized by liquidnebulizers employing either hydraulic or ultrasonic atomization or bymodified micropump systems (like the soft mist inhalers, the Aerodose®or the AERx® systems). Propellant-based systems may use suitablepressurized metered-dose inhalers (pMDIs). Dry powders may use drypowder inhaler devices (DPIs), which are capable of dispersing the drugsubstance effectively. A desired particle size and distribution may beobtained by choosing an appropriate device.

In some embodiments, the compositions of Formula (I) disclosed hereincan be administered to the ear by various methods. For example, a roundwindow catheter (e.g., U.S. Pat. Nos. 6,440,102 and 6,648,873) can beused.

Alternatively, formulations can be incorporated into a wick for usebetween the outer and middle ear (e.g., U.S. Pat. No. 6,120,484) orabsorbed to collagen sponge or other solid support (e.g., U.S. Pat. No.4,164,559).

If desired, formulations of the invention can be incorporated into a gelformulation (e.g., U.S. Pat. Nos. 4,474,752 and 6,911,211).

In some embodiments, compounds of Formula (I) disclosed herein intendedfor delivery to the ear can be administered via an implanted pump anddelivery system through a needle directly into the middle or inner ear(cochlea) or through a cochlear implant stylet electrode channel oralternative prepared drug delivery channel such as but not limited to aneedle through temporal bone into the cochlea.

Other options include delivery via a pump through a thin film coatedonto a multichannel electrode or electrode with a specially imbeddeddrug delivery channel (pathways) carved into the thin film for thispurpose. In other embodiments the acidic or basic solid compound ofFormula (I) can be delivered from the reservoir of an external orinternal implanted pumping system.

Formulations of the invention also can be administered to the ear byintratympanic injection into the middle ear, inner ear, or cochlea(e.g., U.S. Pat. No. 6,377,849 and Ser. No. 11/337,815).

Intratympanic injection of therapeutic agents is the technique ofinjecting a therapeutic agent behind the tympanic membrane into themiddle and/or inner ear. In one embodiment, the formulations describedherein are administered directly onto the round window membrane viatranstympanic injection. In another embodiment, the ion channelmodulating agent auris-acceptable formulations described herein areadministered onto the round window membrane via a non-transtympanicapproach to the inner ear. In additional embodiments, the formulationdescribed herein is administered onto the round window membrane via asurgical approach to the round window membrane comprising modificationof the crista fenestrae cochleae.

In some embodiments, the compounds of Formula (I) are formulated inrectal compositions such as enemas, rectal gels, rectal foams, rectalaerosols, suppositories, jelly suppositories, or retention enemas,containing conventional suppository bases such as cocoa butter or otherglycerides, as well as synthetic polymers such as polyvinylpyrrolidone,PEG (like PEG ointments), and the like.

Suppositories for rectal administration of the drug (either as asolution, colloid, suspension or a complex) can be prepared by mixing acompound provided herein with a suitable non-irritating excipient thatis solid at ordinary temperatures but liquid at the rectal temperatureand will therefore melt or erode/dissolve in the rectum and release thecompound. Such materials include cocoa butter, glycerinated gelatin,hydrogenated vegetable oils, poloxamers, mixtures of polyethyleneglycols of various molecular weights and fatty acid esters ofpolyethylene glycol. In suppository forms of the compositions, alow-melting wax such as, but not limited to, a mixture of fatty acidglycerides, optionally in combination with cocoa butter, is firstmelted.

Solid compositions can be provided in various different types of dosageforms, depending on the physicochemical properties of the compoundprovided herein, the desired dissolution rate, cost considerations, andother criteria. In one of the embodiments, the solid composition is asingle unit. This implies that one unit dose of the compound iscomprised in a single, physically shaped solid form or article. In otherwords, the solid composition is coherent, which is in contrast to amultiple unit dosage form, in which the units are incoherent.

Examples of single units which may be used as dosage forms for the solidcomposition include tablets, such as compressed tablets, film-likeunits, foil-like units, wafers, lyophilized matrix units, and the like.In one embodiment, the solid composition is a highly porous lyophilizedform. Such lyophilizates, sometimes also called wafers or lyophilizedtablets, are particularly useful for their rapid disintegration, whichalso enables the rapid dissolution of the compound.

On the other hand, for some applications the solid composition may alsobe formed as a multiple unit dosage form as defined above. Examples ofmultiple units are powders, granules, microparticles, pellets,mini-tablets, beads, lyophilized powders, and the like. In oneembodiment, the solid composition is a lyophilized powder. Such adispersed lyophilized system comprises a multitude of powder particles,and due to the lyophilization process used in the formation of thepowder, each particle has an irregular, porous microstructure throughwhich the powder is capable of absorbing water very rapidly, resultingin quick dissolution. Effervescent compositions are also contemplated toaid the quick dispersion and absorption of the compound.

Another type of multiparticulate system which is also capable ofachieving rapid drug dissolution is that of powders, granules, orpellets from water-soluble excipients which are coated with a compoundprovided herein so that the compound is located at the outer surface ofthe individual particles. In this type of system, the water-soluble lowmolecular weight excipient may be useful for preparing the cores of suchcoated particles, which can be subsequently coated with a coatingcomposition comprising the compound and, for example, one or moreadditional excipients, such as a binder, a pore former, a saccharide, asugar alcohol, a film-forming polymer, a plasticizer, or otherexcipients used in pharmaceutical coating compositions.

Also provided herein are kits. Typically, a kit includes one or morecompounds or compositions as described herein. In certain embodiments, akit can include one or more delivery systems, e.g., for delivering oradministering a compound as provided herein, and directions for use ofthe kit (e.g., instructions for treating a patient). In anotherembodiment, the kit can include a compound or composition as describedherein and a label that indicates that the contents are to beadministered to a patient with cancer. In another embodiment, the kitcan include a compound or composition as described herein and a labelthat indicates that the contents are to be administered to a patientwith one or more of hepatocellular carcinoma, colon cancer, leukemia,lymphoma, sarcoma, ovarian cancer, diabetic retinopathy, pulmonaryfibrosis, rheumatoid arthritis, sepsis, ankylosing spondylitis,psoriasis, scleroderma, mycotic and viral infections, bone and cartilagediseases, Alzheimer's disease, lung disease, bone/osteoporotic (wrist,spine, shoulder and hip) fractures, articular cartilage (chondral)defects, degenerative disc disease (or intervertebral discdegeneration), polyposis coli, bone density and vascular defects in theeye (Osteoporosis-pseudoglioma Syndrome, OPPG) and other eye diseases orsyndromes associated with defects and/or damaged photoreceptors,familial exudative vitreoretinopathy, retinal angiogenesis, earlycoronary disease, tetra-amelia, Müllerian-duct regression andvirilization, SERKAL syndrome, type II diabetes, Fuhrmann syndrome,Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,odonto-onycho-dermal dysplasia, obesity, split-hand/foot malformation,caudal duplication, tooth agenesis, Wilms tumor, skeletal dysplasia,focal dermal hypoplasia, autosomal recessive anonychia, neural tubedefects, alpha-thalassemia (ATRX) syndrome, fragile X syndrome, ICFsyndrome, Angelman's syndrome, Prader-Willi syndrome, Beckwith-WiedemannSyndrome, Norrie disease, and Rett syndrome.

Methods of Treatment

The compounds and compositions provided herein can be used as inhibitorsand/or modulators of one or more components of the Wnt pathway, whichmay include one or more Wnt proteins, and thus can be used to treat avariety of disorders and diseases in which aberrant Wnt signaling isimplicated, such as cancer and other diseases associated with abnormalangiogenesis, cellular proliferation, and cell cycling. Accordingly, thecompounds and compositions provided herein can be used to treat cancer,to reduce or inhibit angiogenesis, to reduce or inhibit cellularproliferation, to correct a genetic disorder, and/or to treat aneurological condition/disorder/disease due to mutations ordysregulation of the Wnt pathway and/or of one or more of Wnt signalingcomponents. Non-limiting examples of diseases which can be treated withthe compounds and compositions provided herein include a variety ofcancers, diabetic retinopathy, pulmonary fibrosis, rheumatoid arthritis,scleroderma, mycotic and viral infections, bone and cartilage diseases,neurological conditions/diseases such as Alzheimer's disease,amyotrophic lateral sclerosis (ALS), motor neuron disease, multiplesclerosis or autism, lung disease, bone/osteoporotic (wrist, spine,shoulder and hip) fractures, polyposis coli, bone density and vasculardefects in the eye (Osteoporosis-pseudoglioma Syndrome, OPPG) and othereye diseases or syndromes associated with defects and/or damagedphotoreceptors, familial exudative vitreoretinopathy, retinalangiogenesis, early coronary disease, tetra-amelia, Müllerian-ductregression and virilization, SERKAL syndrome, type II diabetes, Fuhrmannsyndrome, Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,odonto-onycho-dermal dysplasia, obesity, split-hand/foot malformation,caudal duplication, tooth agenesis, Wilms tumor, skeletal dysplasia,focal dermal hypoplasia, autosomal recessive anonychia, neural tubedefects, alpha-thalassemia (ATRX) syndrome, fragile X syndrome, ICFsyndrome, Angelman's syndrome, Prader-Willi syndrome, Beckwith-WiedemannSyndrome, Norrie disease and Rett syndrome.

In some embodiments, non-limiting examples of eye diseases which can betreated with the compounds and compositions provided herein includeage-related macular degeneration (AMD or ARMD), rod cone dystrophy,retinitis pigmentosa (RP), acute idiopathic blind spot enlargement(AIBSE), acute zonal occult outer retinopathy (AZOOR), acute macularneuroretinopathy (AMN), multiple evanescent white dot syndrome (MEWDS),multifocal choroiditis, opticneuropathy. Further causes of photoreceptordamage that can be treated with the compounds and compositions providedherein include retinal detachment, vascular disturbance, eye tumors orextreme light damage.

With respect to cancer, the Wnt pathway is known to be constitutivelyactivated in a variety of cancers including, for example, colon cancer,hepatocellular carcinoma, lung cancer, ovarian cancer, prostate cancer,pancreatic cancer and leukemias such as CML, CLL and T-ALL. Accordingly,the compounds and compositions described herein may be used to treatthese cancers in which the Wnt pathway is constitutively activated. Incertain embodiments, the cancer is chosen from hepatocellular carcinoma,colon cancer, leukemia, lymphoma, sarcoma and ovarian cancer.

Other cancers can also be treated with the compounds and compositionsdescribed herein.

More particularly, cancers that may be treated by the compounds,compositions and methods described herein include, but are not limitedto, the following:

1) Breast cancers, including, for example ER⁺ breast cancer, ER⁻ breastcancer, her2⁻ breast cancer, her2⁺ breast cancer, stromal tumors such asfibroadenomas, phyllodes tumors, and sarcomas, and epithelial tumorssuch as large duct papillomas; carcinomas of the breast including insitu (noninvasive) carcinoma that includes ductal carcinoma in situ(including Paget's disease) and lobular carcinoma in situ, and invasive(infiltrating) carcinoma including, but not limited to, invasive ductalcarcinoma, invasive lobular carcinoma, medullary carcinoma, colloid(mucinous) carcinoma, tubular carcinoma, and invasive papillarycarcinoma; and miscellaneous malignant neoplasms. Further examples ofbreast cancers can include luminal A, luminal B, basal A, basal B, andtriple negative breast cancer, which is estrogen receptor negative(ER⁻), progesterone receptor negative, and her2 negative (her2⁻). Insome embodiments, the breast cancer may have a high risk Oncotype score.

2) Cardiac cancers, including, for example sarcoma, e.g., angiosarcoma,fibrosarcoma, rhabdomyosarcoma, and liposarcoma; myxoma; rhabdomyoma;fibroma; lipoma and teratoma.

3) Lung cancers, including, for example, bronchogenic carcinoma, e.g.,squamous cell, undifferentiated small cell, undifferentiated large cell,and adenocarcinoma; alveolar and bronchiolar carcinoma; bronchialadenoma; sarcoma; lymphoma; chondromatous hamartoma; and mesothelioma.

4) Gastrointestinal cancer, including, for example, cancers of theesophagus, e.g., squamous cell carcinoma, adenocarcinoma,leiomyosarcoma, and lymphoma; cancers of the stomach, e.g., carcinoma,lymphoma, and leiomyosarcoma; cancers of the pancreas, e.g., ductaladenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumors,and vipoma; cancers of the small bowel, e.g., adenocarcinoma, lymphoma,carcinoid tumors, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma,neurofibroma, and fibroma; cancers of the large bowel, e.g.,adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, andleiomyoma.

5) Genitourinary tract cancers, including, for example, cancers of thekidney, e.g., adenocarcinoma, Wilm's tumor (nephroblastoma), lymphoma,and leukemia; cancers of the bladder and urethra, e.g., squamous cellcarcinoma, transitional cell carcinoma, and adenocarcinoma; cancers ofthe prostate, e.g., adenocarcinoma, and sarcoma; cancer of the testis,e.g., seminoma, teratoma, embryonal carcinoma, teratocarcinoma,choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma,fibroadenoma, adenomatoid tumors, and lipoma.

6) Liver cancers, including, for example, hepatoma, e.g., hepatocellularcarcinoma; cholangiocarcinoma; hepatoblastoma; angiosarcoma;hepatocellular adenoma; and hemangioma.

7) Bone cancers, including, for example, osteogenic sarcoma(osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma,chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cellsarcoma), multiple myeloma, malignant giant cell tumor chordoma,osteochrondroma (osteocartilaginous exostoses), benign chondroma,chondroblastoma, chondromyxofibroma, osteoid osteoma and giant celltumors.

8) Nervous system cancers, including, for example, cancers of the skull,e.g., osteoma, hemangioma, granuloma, xanthoma, and osteitis deformans;cancers of the meninges, e.g., meningioma, meningiosarcoma, andgliomatosis; cancers of the brain, e.g., astrocytoma, medulloblastoma,glioma, ependymoma, germinoma (pinealoma), glioblastoma multiform,oligodendroglioma, schwannoma, retinoblastoma, and congenital tumors;and cancers of the spinal cord, e.g., neurofibroma, meningioma, glioma,and sarcoma.

9) Gynecological cancers, including, for example, cancers of the uterus,e.g., endometrial carcinoma; cancers of the cervix, e.g., cervicalcarcinoma, and pre tumor cervical dysplasia; cancers of the ovaries,e.g., ovarian carcinoma, including serous cystadenocarcinoma, mucinouscystadenocarcinoma, unclassified carcinoma, granulosa theca cell tumors,Sertoli Leydig cell tumors, dysgerminoma, and malignant teratoma;cancers of the vulva, e.g., squamous cell carcinoma, intraepithelialcarcinoma, adenocarcinoma, fibrosarcoma, and melanoma; cancers of thevagina, e.g., clear cell carcinoma, squamous cell carcinoma, botryoidsarcoma, and embryonal rhabdomyosarcoma; and cancers of the fallopiantubes, e.g., carcinoma.

10) Hematologic cancers, including, for example, cancers of the blood,e.g., acute myeloid leukemia, chronic myeloid leukemia, acutelymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferativediseases, multiple myeloma, and myelodysplastic syndrome, Hodgkin'slymphoma, non-Hodgkin's lymphoma (malignant lymphoma) and Waldenstrom'smacroglobulinemia.

11) Skin cancers and skin disorders, including, for example, malignantmelanoma and metastatic melanoma, basal cell carcinoma, squamous cellcarcinoma, Kaposi's sarcoma, moles dysplastic nevi, lipoma, angioma,dermatofibroma, keloids, and scleroderma.

12) Adrenal gland cancers, including, for example, neuroblastoma.

Cancers may be solid tumors that may or may not be metastatic. Cancersmay also occur, as in leukemia, as a diffuse tissue. Thus, the term“tumor cell,” as provided herein, includes a cell afflicted by any oneof the above identified disorders.

A method of treating cancer using a compound or composition as describedherein may be combined with existing methods of treating cancers, forexample by chemotherapy, irradiation, or surgery (e.g., oophorectomy).In some embodiments, a compound or composition can be administeredbefore, during, or after another anticancer agent or treatment.

The compounds and compositions described herein can be used asanti-angiogenesis agents and as agents for modulating and/or inhibitingthe activity of protein kinases, thus providing treatments for cancerand other diseases associated with cellular proliferation mediated byprotein kinases. For example, the compounds described herein can inhibitthe activity of one or more kinases. Accordingly, provided herein is amethod of treating cancer or preventing or reducing angiogenesis throughkinase inhibition.

In addition, and including treatment of cancer, the compounds andcompositions described herein can function as cell-cycle control agentsfor treating proliferative disorders in a patient. Disorders associatedwith excessive proliferation include, for example, cancers, scleroderma,immunological disorders involving undesired proliferation of leukocytes,and restenosis and other smooth muscle disorders. Furthermore, suchcompounds may be used to prevent de-differentiation of post-mitotictissue and/or cells.

Diseases or disorders associated with uncontrolled or abnormal cellularproliferation include, but are not limited to, the following:

-   -   a variety of cancers, including, but not limited to, carcinoma,        hematopoietic tumors of lymphoid lineage, hematopoietic tumors        of myeloid lineage, tumors of mesenchymal origin, tumors of the        central and peripheral nervous system and other tumors including        melanoma, seminoma and Kaposi's sarcoma.    -   a disease process which features abnormal cellular        proliferation, e.g., benign prostatic hyperplasia, familial        adenomatosis polyposis, neurofibromatosis, atherosclerosis,        arthritis, glomerulonephritis, restenosis following angioplasty        or vascular surgery, inflammatory bowel disease, transplantation        rejection, endotoxic shock, and fungal infections. Fibrotic        disorders such as skin fibrosis; scleroderma; progressive        systemic fibrosis; lung fibrosis; muscle fibrosis; kidney        fibrosis; glomerulosclerosis; glomerulonephritis; hypertrophic        scar formation; uterine fibrosis; renal fibrosis; cirrhosis of        the liver, liver fibrosis; fatty liver disease (FLD); adhesions,        such as those occurring in the abdomen, pelvis, spine or        tendons; chronic obstructive pulmonary disease; fibrosis        following myocardial infarction; pulmonary fibrosis; fibrosis        and scarring associated with diffuse/interstitial lung disease;        central nervous system fibrosis, such as fibrosis following        stroke; fibrosis associated with neuro-degenerative disorders        such as Alzheimer's Disease or multiple sclerosis; fibrosis        associated with proliferative vitreoretinopathy (PVR);        restenosis; endometriosis; ischemic disease and radiation        fibrosis.    -   defective apoptosis-associated conditions, such as cancers        (including but not limited to those types mentioned herein),        viral infections (including but not limited to herpesvirus,        poxvirus, Epstein-Barr virus, Sindbis virus and adenovirus),        prevention of AIDS development in HIV-infected individuals,        autoimmune diseases (including but not limited to systemic lupus        erythematosus, rheumatoid arthritis, sepsis, ankylosing        spondylitis, psoriasis, scleroderma, autoimmune mediated        glomerulonephritis, inflammatory bowel disease and autoimmune        diabetes mellitus), neuro-degenerative disorders (including but        not limited to Alzheimer's disease, lung disease, amyotrophic        lateral sclerosis, retinitis pigmentosa, Parkinson's disease,        AIDS-related dementia, spinal muscular atrophy and cerebellar        degeneration), myelodysplastic syndromes, aplastic anemia,        ischemic injury associated with myocardial infarctions, stroke        and reperfusion injury, arrhythmia, atherosclerosis,        toxin-induced or alcohol related liver diseases, hematological        diseases (including but not limited to chronic anemia and        aplastic anemia), degenerative diseases of the musculoskeletal        system (including but not limited to osteoporosis and        arthritis), tendinopathies such as tendinitis and tendinosis,        aspirin-sensitive rhinosinusitis, cystic fibrosis, multiple        sclerosis, kidney diseases and cancer pain.    -   genetic diseases due to mutations in Wnt signaling components,        such as polyposis coli, bone density and vascular defects in the        eye (Osteoporosis-pseudoglioma Syndrome, OPPG) and other eye        diseases or syndromes associated with defects and/or damaged        photoreceptors, familial exudative vitreoretinopathy, retinal        angiogenesis, early coronary disease, tetra-amelia,        Müllerian-duct regression and virilization, SERKAL syndrome,        type II diabetes, Fuhrmann syndrome,        Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,        odonto-onycho-dermal dysplasia, obesity, split-hand/foot        malformation, caudal duplication, tooth agenesis, Wilms tumor,        skeletal dysplasia, focal dermal hypoplasia, autosomal recessive        anonychia, neural tube defects, alpha-thalassemia (ATRX)        syndrome, fragile X syndrome, ICF syndrome, Angelman's syndrome,        Prader-Willi syndrome, Beckwith-Wiedemann Syndrome, Norrie        disease and Rett syndrome.

The compounds and compositions described herein can be used to treatneurological conditions, disorders and/or diseases caused by dysfunctionin the Wnt signaling pathway. Non-limiting examples of neurologicalconditions/disorders/diseases which can be treated with the compoundsand compositions provided herein include Alzheimer's disease, aphasia,apraxia, arachnoiditis, ataxia telangiectasia, attention deficithyperactivity disorder, auditory processing disorder, autism,alcoholism, Bell's palsy, bipolar disorder, brachial plexus injury,Canavan disease, carpal tunnel syndrome, causalgia, central painsyndrome, central pontine myelinolysis, centronuclear myopathy, cephalicdisorder, cerebral aneurysm, cerebral arteriosclerosis, cerebralatrophy, cerebral gigantism, cerebral palsy, cerebral vasculitis,cervical spinal stenosis, Charcot-Marie-Tooth disease, Chiarimalformation, chronic fatigue syndrome, chronic inflammatorydemyelinating polyneuropathy (CIDP), chronic pain, CoffinLowry syndrome,complex regional pain syndrome, compression neuropathy, congenitalfacial diplegia, corticobasal degeneration, cranial arteritis,craniosynostosis, Creutzfeldt-Jakob disease, cumulative trauma disorder,Cushing's syndrome, cytomegalic inclusion body disease (CIBD),Dandy-Walker syndrome, Dawson disease, de Morsier's syndrome,Dejerine-Klumpke palsy, Dejerine-Sottas disease, delayed sleep phasesyndrome, dementia, dermatomyositis, developmental dyspraxia, diabeticneuropathy, diffuse sclerosis, Dravet syndrome, dysautonomia,dyscalculia, dysgraphia, dyslexia, dystonia, empty sella syndrome,encephalitis, encephalocele, encephalotrigeminal angiomatosis,encopresis, epilepsy, Erb's palsy, erythromelalgia, essential tremor,Fabry's disease, Fahr's syndrome, familial spastic paralysis, febrileseizure, Fisher syndrome, Friedreich's ataxia, fibromyalgia, Foville'ssyndrome, Gaucher's disease, Gerstmann's syndrome, giant cell arteritis,giant cell inclusion disease, globoid cell leukodystrophy, gray matterheterotopia, Guillain-Barré syndrome, HTLV-1 associated myelopathy,Hallervorden-Spatz disease, hemifacial spasm, hereditary spasticparaplegia, heredopathia atactica polyneuritiformis, herpes zosteroticus, herpes zoster, Hirayama syndrome, holoprosencephaly,Huntington's disease, hydranencephaly, hydrocephalus, hypercortisolism,hypoxia, immune-mediated encephalomyelitis, inclusion body myositis,incontinentia pigmenti, infantile phytanic acid storage disease,infantile Refsum disease, infantile spasms, inflammatory myopathy,intracranial cyst, intracranial hypertension, Joubert syndrome, Karaksyndrome, Kearns-Sayre syndrome, Kennedy disease, Kinsbourne syndrome,Klippel Feil syndrome, Krabbe disease, Kugelberg-Welander disease, kuru,Lafora disease, Lambert-Eaton myasthenic syndrome, Landau-Kleffnersyndrome, lateral medullary (Wallenberg) syndrome, Leigh's disease,Lennox-Gastaut syndrome, Lesch-Nyhan syndrome, leukodystrophy, Lewy bodydementia, lissencephaly, locked-in syndrome, Lou Gehrig's disease,lumbar disc disease, lumbar spinal stenosis, Lyme disease,Machado-Joseph disease (Spinocerebellar ataxia type 3), macrencephaly,macropsia, megalencephaly, Melkersson-Rosenthal syndrome, Meniere'sdisease, meningitis, Menkes disease, metachromatic leukodystrophy,microcephaly, micropsia, Miller Fisher syndrome, misophonia,mitochondrial myopathy, Mobius syndrome, monomelic amyotrophy, motorneuron disease, motor skills disorder, Moyamoya disease,mucopolysaccharidoses, multi-infarct dementia, multifocal motorneuropathy, multiple sclerosis, multiple system atrophy, musculardystrophy, myalgic encephalomyelitis, myasthenia gravis, myelinoclasticdiffuse sclerosis, myoclonic Encephalopathy of infants, myoclonus,myopathy, myotubular myopathy, myotonia congenital, narcolepsy,neurofibromatosis, neuroleptic malignant syndrome, lupus erythematosus,neuromyotonia, neuronal ceroid lipofuscinosis, Niemann-Pick disease,O'Sullivan-McLeod syndrome, occipital Neuralgia, occult SpinalDysraphism Sequence, Ohtahara syndrome, olivopontocerebellar atrophy,opsoclonus myoclonus syndrome, optic neuritis, orthostatic hypotension,palinopsia, paresthesia, Parkinson's disease, paramyotonia Congenita,paraneoplastic diseases, paroxysmal attacks, Parry-Romberg syndrome,Pelizaeus-Merzbacher disease, periodic paralyses, peripheral neuropathy,photic sneeze reflex, phytanic acid storage disease, Pick's disease,polymicrogyria (PMG), polymyositis, porencephaly, post-polio syndrome,postherpetic neuralgia (PHN), postural hypotension, Prader-Willisyndrome, primary lateral sclerosis, prion diseases, progressivehemifacial atrophy, progressive multifocal leukoencephalopathy,progressive supranuclear palsy, pseudotumor cerebri, Ramsay Huntsyndrome type I, Ramsay Hunt syndrome type II, Ramsay Hunt syndrome typeIII, Rasmussen's encephalitis, reflex neurovascular dystrophy, Refsumdisease, restless legs syndrome, retrovirus-associated myelopathy, Rettsyndrome, Reye's syndrome, rhythmic movement disorder, Romberg syndrome,Saint Vitus dance, Sandhoff disease, schizophrenia, Schilder's disease,schizencephaly, sensory integration dysfunction, septo-optic dysplasia,Shy-Drager syndrome, Sjögren's syndrome, snatiation, Sotos syndrome,spasticity, spina bifida, spinal cord tumors, spinal muscular atrophy,spinocerebellar ataxia, Steele-Richardson-Olszewski syndrome,Stiff-person syndrome, stroke, Sturge-Weber syndrome, subacutesclerosing panencephalitis, subcortical arteriosclerotic encephalopathy,superficial siderosis, Sydenham's chorea, syncope, synesthesia,syringomyelia, tarsal tunnel syndrome, tardive dyskinesia, tardivedysphrenia, Tarlov cyst, Tay-Sachs disease, temporal arteritis, tetanus,tethered spinal cord syndrome, Thomsen disease, thoracic outletsyndrome, tic douloureux, Todd's paralysis, Tourette syndrome, toxicencephalopathy, transient ischemic attack, transmissible spongiformencephalopathies, transverse myelitis, tremor, trigeminal neuralgia,tropical spastic paraparesis, trypanosomiasis, tuberous sclerosis,ubisiosis, Von Hippel-Lindau disease (VHL), Viliuisk Encephalomyelitis(VE), Wallenberg's syndrome, Werdnig, Hoffman disease, west syndrome,Williams syndrome, Wilson's disease and Zellweger syndrome.

The compounds and compositions may also be useful in the inhibition ofthe development of invasive cancer, tumor angiogenesis and metastasis.

In some embodiments, the disclosure provides a method for treating adisease or disorder associated with aberrant cellular proliferation byadministering to a patient in need of such treatment an effective amountof one or more of the compounds of Formula (I), in combination(simultaneously or sequentially) with at least one other agent.

In some embodiments, the disclosure provides a method of treating orameliorating in a patient a disorder or disease selected from the groupconsisting of: cancer, pulmonary fibrosis, idiopathic pulmonary fibrosis(IPF), degenerative disc disease, bone/osteoporotic fractures, bone orcartilage disease, and osteoarthritis, the method comprisingadministering to the patient a therapeutically effective amount of acompound according to claim 1, or a pharmaceutically acceptable saltthereof.

In some embodiments, the pharmaceutical composition comprises atherapeutically effective amount of a compound of Formula (I), or apharmaceutically acceptable salt thereof, and a pharmaceuticallyacceptable excipient.

In some embodiments, the method of treats a disorder or disease in whichaberrant Wnt signaling is implicated in a patient, the method comprisesadministering to the patient a therapeutically effective amount of acompound of Formula (I), or a pharmaceutically acceptable salt thereof.

In some embodiments, the disorder or disease is cancer.

In some embodiments, the disorder or disease is systemic inflammation.

In some embodiments, the disorder or disease is metastatic melanoma.

In some embodiments, the disorder or disease is fatty liver disease.

In some embodiments, the disorder or disease is liver fibrosis.

In some embodiments, the disorder or disease is tendonitis.

In some embodiments, the disorder or disease is damage to a tendonrequiring tendon regeneration.

In some embodiments, the disorder or disease is diabetes.

In some embodiments, the disorder or disease is degenerative discdisease.

In some embodiments, the disorder or disease is osteoarthritis.

In some embodiments, the disorder or disease is diabetic retinopathy.

In some embodiments, the disorder or disease is pulmonary fibrosis.

In some embodiments, the disorder or disease is idiopathic pulmonaryfibrosis (IPF).

In some embodiments, the disorder or disease is degenerative discdisease.

In some embodiments, the disorder or disease is rheumatoid arthritis.

In some embodiments, the disorder or disease is scleroderma.

In some embodiments, the disorder or disease is a mycotic or viralinfection.

In some embodiments, the disorder or disease is a bone or cartilagedisease.

In some embodiments, the disorder or disease is Alzheimer's disease.

In some embodiments, the disorder or disease is osteoarthritis.

In some embodiments, the disorder or disease is lung disease

In some embodiments, the disorder or disease is a genetic disease causedby mutations in Wnt signaling components, wherein the genetic disease isselected from: polyposis coli, osteoporosis-pseudoglioma syndrome,familial exudative vitreoretinopathy, retinal angiogenesis, earlycoronary disease, tetra-amelia syndrome, Müllerian-duct regression andvirilization, SERKAL syndrome, diabetes mellitus type 2, Fuhrmannsyndrome, Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,odonto-onycho-dermal dysplasia, obesity, split-hand/foot malformation,caudal duplication syndrome, tooth agenesis, Wilms tumor, skeletaldysplasia, focal dermal hypoplasia, autosomal recessive anonychia,neural tube defects, alpha-thalassemia (ATRX) syndrome, fragile Xsyndrome, ICF syndrome, Angelman syndrome, Prader-Willi syndrome,Beckwith-Wiedemann Syndrome, Norrie disease and Rett syndrome.

In some embodiments, the patient is a human.

In some embodiments, the cancer is chosen from: hepatocellularcarcinoma, colon cancer, breast cancer, pancreatic cancer, chronicmyeloid leukemia (CML), chronic myelomonocytic leukemia, chroniclymphocytic leukemia (CLL), acute myeloid leukemia, acute lymphocyticleukemia, Hodgkin lymphoma, lymphoma, sarcoma and ovarian cancer.

In some embodiments, the cancer is chosen from: lung cancer—non-smallcell, lung cancer—small cell, multiple myeloma, nasopharyngeal cancer,neuroblastoma, osteosarcoma, penile cancer, pituitary tumors, prostatecancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, skincancer—basal and squamous cell, skin cancer—melanoma, small intestinecancer, stomach (gastric) cancers, testicular cancer, thymus cancer,thyroid cancer, uterine sarcoma, vaginal cancer, vulvar cancer,laryngeal or hypopharyngeal cancer, kidney cancer, Kaposi sarcoma,gestational trophoblastic disease, gastrointestinal stromal tumor,gastrointestinal carcinoid tumor, gallbladder cancer, eye cancer(melanoma and lymphoma), Ewing tumor, esophagus cancer, endometrialcancer, colorectal cancer, cervical cancer, brain or spinal cord tumor,bone metastasis, bone cancer, bladder cancer, bile duct cancer, analcancer and adrenal cortical cancer.

In some embodiments, the cancer is hepatocellular carcinoma.

In some embodiments, the cancer is colon cancer.

In some embodiments, the cancer is colorectal cancer.

In some embodiments, the cancer is breast cancer.

In some embodiments, the cancer is pancreatic cancer.

In some embodiments, the cancer is chronic myeloid leukemia (CML).

In some embodiments, the cancer is chronic myelomonocytic leukemia.

In some embodiments, the cancer is chronic lymphocytic leukemia (CLL).

In some embodiments, the cancer is acute myeloid leukemia.

In some embodiments, the cancer is acute lymphocytic leukemia.

In some embodiments, the cancer is Hodgkin lymphoma.

In some embodiments, the cancer is lymphoma.

In some embodiments, the cancer is sarcoma.

In some embodiments, the cancer is ovarian cancer.

In some embodiments, the cancer is lung cancer—non-small cell.

In some embodiments, the cancer is lung cancer—small cell.

In some embodiments, the cancer is multiple myeloma.

In some embodiments, the cancer is nasopharyngeal cancer.

In some embodiments, the cancer is neuroblastoma.

In some embodiments, the cancer is osteosarcoma.

In some embodiments, the cancer is penile cancer.

In some embodiments, the cancer is pituitary tumors.

In some embodiments, the cancer is prostate cancer.

In some embodiments, the cancer is retinoblastoma.

In some embodiments, the cancer is rhabdomyosarcoma.

In some embodiments, the cancer is salivary gland cancer.

In some embodiments, the cancer is skin cancer—basal and squamous cell.

In some embodiments, the cancer is skin cancer—melanoma.

In some embodiments, the cancer is small intestine cancer.

In some embodiments, the cancer is stomach (gastric) cancers.

In some embodiments, the cancer is testicular cancer.

In some embodiments, the cancer is thymus cancer.

In some embodiments, the cancer is thyroid cancer.

In some embodiments, the cancer is uterine sarcoma.

In some embodiments, the cancer is vaginal cancer.

In some embodiments, the cancer is vulvar cancer.

In some embodiments, the cancer is Wilms tumor.

In some embodiments, the cancer is laryngeal or hypopharyngeal cancer.

In some embodiments, the cancer is kidney cancer.

In some embodiments, the cancer is Kaposi sarcoma.

In some embodiments, the cancer is gestational trophoblastic disease.

In some embodiments, the cancer is gastrointestinal stromal tumor.

In some embodiments, the cancer is gastrointestinal carcinoid tumor.

In some embodiments, the cancer is gallbladder cancer.

In some embodiments, the cancer is eye cancer (melanoma and lymphoma).

In some embodiments, the cancer is Ewing tumor.

In some embodiments, the cancer is esophagus cancer.

In some embodiments, the cancer is endometrial cancer.

In some embodiments, the cancer is colorectal cancer.

In some embodiments, the cancer is cervical cancer.

In some embodiments, the cancer is brain or spinal cord tumor.

In some embodiments, the cancer is bone metastasis.

In some embodiments, the cancer is bone cancer.

In some embodiments, the cancer is bladder cancer.

In some embodiments, the cancer is bile duct cancer.

In some embodiments, the cancer is anal cancer.

In some embodiments, the cancer is adrenal cortical cancer.

In some embodiments, the disorder or disease is a neurologicalcondition, disorder or disease, wherein the neurologicalcondition/disorder/disease is selected from: Alzheimer's disease,frontotemporal dementias, dementia with lewy bodies, prion diseases,Parkinson's disease, Huntington's disease, progressive supranuclearpalsy, corticobasal degeneration, multiple system atrophy, amyotrophiclateral sclerosis (ALS), inclusion body myositis, autism, degenerativemyopathies, diabetic neuropathy, other metabolic neuropathies, endocrineneuropathies, orthostatic hypotension, multiple sclerosis andCharcot-Marie-Tooth disease.

In some embodiments, the compound of Formula (I) inhibits one or moreproteins in the Wnt pathway.

In some embodiments, the compound of Formula (I) inhibits signalinginduced by one or more Wnt proteins.

In some embodiments, the Wnt proteins are chosen from: WNT1, WNT2,WNT2B, WNT3, WNT3A, WNT4. WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A,WNT8B, WNT9A, WNT9B, WNT10A, WNT10B, WNT11, and WNT16.

In some embodiments, the method inhibits one or more proteins in the Wntpathway, the method comprises contacting a cell with an effective amountof a compound of Formula (I).

In some embodiments, the cell is a human cell.

In some embodiments, the human cell is a cancerous cell.

In some embodiments, the cancerous cell is a colon cancer cell.

In some embodiments, the contacting is in vitro.

In some embodiments, the compound of Formula (I) inhibits a kinaseactivity.

In some embodiments, the method treats a disease or disorder mediated bythe Wnt pathway in a patient, the method comprises administering to thepatient a therapeutically effective amount of a compound (or compounds)of Formula (I), or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) inhibits one or moreWnt proteins.

In some embodiments, the method treats a disease or disorder mediated bykinase activity in a patient, the method comprises administering to thepatient a therapeutically effective amount of a compound (or compounds)of Formula (I), or a pharmaceutically acceptable salt thereof.

In some embodiments, the disease or disorder comprises tumor growth,cell proliferation, or angiogenesis.

In some embodiments, the method inhibits the activity of a proteinkinase receptor, the method comprises contacting the receptor with aneffective amount of a compound (or compounds) of Formula (I), or apharmaceutically acceptable salt thereof.

In some embodiments, the method treats a disease or disorder associatedwith aberrant cellular proliferation in a patient; the method comprisesadministering to the patient a therapeutically effective amount of acompound (or compounds) of Formula (I), or a pharmaceutically acceptablesalt thereof.

In some embodiments, the method prevents or reduces angiogenesis in apatient; the method comprises administering to the patient atherapeutically effective amount of a compound (or compounds) of Formula(I), or a pharmaceutically acceptable salt thereof.

In some embodiments, the method prevents or reduces abnormal cellularproliferation in a patient; the method comprises administering to thepatient a therapeutically effective amount of a compound (or compounds)of Formula (I), or a pharmaceutically acceptable salt thereof.

In some embodiments, the method treats a disease or disorder associatedwith aberrant cellular proliferation in a patient, the method comprisesadministering to the patient a pharmaceutical composition comprising oneor more of the compounds of claim 1 in combination with apharmaceutically acceptable carrier and one or more other agents.

Moreover, the compounds and compositions, for example, as inhibitors ofthe cyclin-dependent kinases (CDKs), can modulate the level of cellularRNA and DNA synthesis and therefore are expected to be useful in thetreatment of viral infections such as HIV, human papilloma virus, herpesvirus, Epstein-Barr virus, adenovirus, Sindbis virus, pox virus and thelike.

Compounds and compositions described herein can inhibit the kinaseactivity of, for example, CDK/cyclin complexes, such as those active inthe G₀. or G.₁ stage of the cell cycle, e.g., CDK2, CDK4, and/or CDK6complexes.

Evaluation of Biological Activity

The biological activity of the compounds described herein can be testedusing any suitable assay known to those of skill in the art, see, e.g.,WO 2001/053268 and WO 2005/009997. For example, the activity of acompound may be tested using one or more of the test methods outlinedbelow.

In one example, tumor cells may be screened for Wnt independent growth.In such a method, tumor cells of interest are contacted with a compound(i.e. inhibitor) of interest, and the proliferation of the cells, e.g.by uptake of tritiated thymidine, is monitored. In some embodiments,tumor cells may be isolated from a candidate patient who has beenscreened for the presence of a cancer that is associated with a mutationin the Wnt signaling pathway. Candidate cancers include, withoutlimitation, those listed above.

In another example, one may utilize in vitro assays for Wnt biologicalactivity, e.g. stabilization of β-catenin and promoting growth of stemcells. Assays for biological activity of Wnt include stabilization ofβ-catenin, which can be measured, for example, by serial dilutions of acandidate inhibitor composition. An exemplary assay for Wnt biologicalactivity contacts a candidate inhibitor with cells containingconstitutively active Wnt/β-catenin signaling. The cells are culturedfor a period of time sufficient to stabilize β-catenin, usually at leastabout 1 hour, and lysed. The cell lysate is resolved by SDS PAGE, thentransferred to nitrocellulose and probed with antibodies specific forβ-catenin.

In a further example, the activity of a candidate compound can bemeasured in a Xenopus secondary axis bioassay (Leyns, L. et al. Cell(1997), 88(6), 747-756).

To further illustrate this invention, the following examples areincluded. The examples should not, of course, be construed asspecifically limiting the invention. Variations of these examples withinthe scope of the claims are within the purview of one skilled in the artand are considered to fall within the scope of the invention asdescribed, and claimed herein. The reader will recognize that theskilled artisan, armed with the present disclosure, and skill in the artis able to prepare and use the invention without exhaustive examples.

EXAMPLES Compound Preparation

The starting materials used in preparing the compounds of the inventionare known, made by known methods, or are commercially available. It willbe apparent to the skilled artisan that methods for preparing precursorsand functionality related to the compounds claimed herein are generallydescribed in the literature. The skilled artisan given the literatureand this disclosure is well equipped to prepare any of the compounds.

It is recognized that the skilled artisan in the art of organicchemistry can readily carry out manipulations without further direction,that is, it is well within the scope and practice of the skilled artisanto carry out these manipulations. These include reduction of carbonylcompounds to their corresponding alcohols, oxidations, acylations,aromatic substitutions, both electrophilic and nucleophilic,etherifications, esterification and saponification and the like. Thesemanipulations are discussed in standard texts such as March's AdvancedOrganic Chemistry: Reactions, Mechanisms, and Structure 7^(th) Ed., JohnWiley & Sons (2013), Carey and Sundberg, Advanced Organic Chemistry5^(th) Ed., Springer (2007), Comprehensive Organic Transformations: AGuide to Functional Group Transformations, 2^(nd) Ed., John Wiley & Sons(1999) (incorporated herein by reference in its entirety) and the like.

The skilled artisan will readily appreciate that certain reactions arebest carried out when other functionality is masked or protected in themolecule, thus avoiding any undesirable side reactions and/or increasingthe yield of the reaction. Often the skilled artisan utilizes protectinggroups to accomplish such increased yields or to avoid the undesiredreactions. These reactions are found in the literature and are also wellwithin the scope of the skilled artisan. Examples of many of thesemanipulations can be found for example in T. Greene and P. WutsProtective Groups in Organic Synthesis, 4th Ed., John Wiley & Sons(2007), incorporated herein by reference in its entirety.

Trademarks used herein are examples only and reflect illustrativematerials used at the time of the invention. The skilled artisan willrecognize that variations in lot, manufacturing processes, and the like,are expected. Hence the examples, and the trademarks used in them arenon-limiting, and they are not intended to be limiting, but are merelyan illustration of how a skilled artisan may choose to perform one ormore of the embodiments of the invention.

(¹H) nuclear magnetic resonance spectra (NMR) were measured in theindicated solvents on a Bruker NMR spectrometer (Avance™ DRX300, 300 MHzfor ¹H or Avance™ DRX500, 500 MHz for ¹H) or Varian NMR spectrometer(Mercury 400BB, 400 MHz for ¹H). Peak positions are expressed in partsper million (ppm) downfield from tetramethylsilane. The peakmultiplicities are denoted as follows, s, singlet; d, doublet; t,triplet; q, quartet; ABq, AB quartet; quin, quintet; sex, sextet; sep,septet; non, nonet; dd, doublet of doublets; ddd, doublet of doublets ofdoublets; d/ABq, doublet of AB quartet; dt, doublet of triplets; td,triplet of doublets; dq, doublet of quartets; m, multiplet.

The following abbreviations have the indicated meanings:

BH₃-Me₂S=borane dimethyl sulfide complex

(Boc)₂O=di-tert-butyl dicarbonate

brine=saturated aqueous sodium chloride

CDCl₃=deuterated chloroform

CD₃OD=deuterated methanol

DCAD=di-(4-chlorobenzyl)azodicarboxylate

DCE=dichloroethane

DCM=dichloromethane

DEAD=diethyl azodicarboxylate

DHP=dihydropyran

DMAP=4-dimethylaminopyridine

DMF=N,N-dimethylformamide

DMSO-d₆=deuterated dimethylsulfoxide

ESIMS=electron spray mass spectrometry

EtOAc=ethyl acetate

EtOH=ethanol

HCl=hydrochloric acid

HOAc=acetic acid

K₂CO₃=potassium carbonate

KOAc=potassium acetate

LDA=lithium diisopropylamide

LC/MS=liquid chromatography—mass spectrometry

MeOH=methanol

MgSO₄=magnesium sulfate

MsCl=methanesulfonyl chloride or mesyl chloride

MW=microwave

NaBH₄=sodium borohydride

NaBH(OAc)₃=sodium triacetoxyborohydride

NaCNBH₃=sodium cyanoborohydride

NaHCO₃=sodium bicarbonate

NaOH=sodium hydroxide

Na₂S₂O₅=sodium metabisulfite or sodium pyrosulfite

NH₄OH=ammonium hydroxide

NMR=nuclear magnetic resonance

ON=overnight

Pd/C=palladium(0) on carbon

Pd(dppf)Cl₂=1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride

Pd(PPh₃)₄=tetrakis(triphenylphosphine)palladium(0)

Pd(PPh₃)₂Cl₂=bis(triphenylphosphine)palladium(II) dichloride

PE=petroleum ether

Pin₂B₂=bis(pinacolato)diboron

PPh₃=triphenylphosphine

PPTS=pyridinium p-toluenesulfonate

r.t.=room temperature

SEM-Cl=2-(trimethylsilyl)ethoxymethyl chloride

TEA=triethylamine

TFA=trifluoroacetic acid

THF=tetrahydrofuran

THP=tetrahydropyran

TLC=thin layer chromatography

p-TsOH=p-toluenesulfonic acid

The following example schemes are provided for the guidance of thereader, and collectively represent an example method for making thecompounds provided herein. Furthermore, other methods for preparingcompounds of the invention will be readily apparent to the person ofordinary skill in the art in light of the following reaction schemes andexamples. The skilled artisan is thoroughly equipped to prepare thesecompounds by those methods given the literature and this disclosure. Thecompound numberings used in the synthetic schemes depicted below aremeant for those specific schemes only, and should not be construed as orconfused with same numberings in other sections of the application.Unless otherwise indicated, all variables are as defined above.

General Procedure

Compounds of Formula (I) of the present invention can be prepared asdepicted in Scheme 1.

Scheme 1 describes a method for preparation of1H-pyrazolo[3,4-c]pyridine derivatives (XI) by first acylating a2-bromo-5-fluoropyridine (II) with an ethyl 2,2-dialkoxyacetate toproduce the acetal protected oxoacetaldehyde (III). The keto group wasthen converted to the Boc-protected hydrazone (IV) followed by basecyclization to the 1H-pyrazolo[3,4-c]pyridine (V). The pyrazolopyridine(V) is then protected with either a Boc or THP (VI) followed by Suzukicoupling with various boronic acids (VII). The pyrazolopyridine acetyl(VIII) is reacted with various 1,2-diamines (IX) to produce (X). Finaldeprotection of the pyrazole nitrogen yields the desired1H-pyrazolo[3,4-c]pyridine derivatives (XI).

Illustrative Compound Examples

Preparation of Boc-protected intermediate (XVI) is depicted below inScheme 2.

Step 1

To a solution of 2-bromo-5-fluoro-pyridine (XII) (100.0 g, 568.21 mmol,1.0 eq) in THF (1000 mL) was added a solution of LDA (66.95 g, 625.04mmol, 1.10 eq) drop-wise at −78° C. over a period of 1 h under N₂. Thereaction mixture was stirred at −78° C. for 30 min. Then a solution ofethyl 2,2-diethoxyacetate (120.15 g, 681.86 mmol, 1.20 eq) was added at−78° C. over a period of 1 h. The reaction mixture was stirred at −78°C. for another 1 h. TLC (PE:EtOAc=10:1) showed that the startingmaterial was consumed completely. The reaction was quenched by NH₄Clslowly and then extracted with EtOAc (1000 mL×2). The combined organicphase was washed with saturated brine (500 mL×2), dried over anhydrousNa₂SO₄, filtered and concentrated in vacuo. The residue was purified bychromatography on silica gel (PE:EtOAc=10:1) to give1-(2-bromo-5-fluoropyridin-4-yl)-2,2-diethoxyethan-1-one (XIII) (160.0g, 522.65 mmol, 92.0% yield) as a yellow solid. ¹H NMR (CDCl₃, 400 MHz)δ ppm 1.26 (t, J=6.8 Hz, 6H), 3.69 (q, J=7.2 Hz, 2H), 3.79 (q, J=7.2 Hz,2H), 5.23 (d, J=2 Hz, 1H), 7.85 (d, J=4.8 Hz, 1H), 8.39 (d, J=1.2 Hz,1H); ESIMS found for C₁₁H₁₃BrFNO₃ m/z 306.1 (M+H).

Step 2

To a mixture of 1-(2-bromo-5-fluoropyridin-4-yl)-2,2-diethoxyethan-1-one(XIII) (142.0 g, 463.86 mmol, 1.0 eq) in THF (2 L) tert-butylhydrazinecarboxylate (61.30 g, 463.86 mmol, 1.0 eq) in one portion atroom temperature. The mixture was stirred at 55° C. for 60 h. TLC(PE:EtOAc=2:1) showed that most of the starting material was consumed.The crude mixture of tert-butyl2-(1-(2-bromo-5-fluoropyridin-4-yl)-2,2-diethoxyethylidene)hydrazine-1-carboxylate(XIV) was used in the next step without further purification.

Step 3

To a solution of tert-butyl2-(1-(2-bromo-5-fluoropyridin-4-yl)-2,2-diethoxyethylidene)hydrazine-1-carboxylate(XIV) (190.0 g, 452.09 mmol, 1.0 eq) in THF (2 L) was added NaH (36.17g, 904.18 mmol, 2.0 eq) in portions at 0° C. over 0.5 h. The mixture wasstirred at 55° C. for 4 hours. TLC (PE:EtOAc=2:1) showed the materialwas consumed completely. The mixture was cooled to 0° C. The mixture waspoured into 10% aqueous NH₄Cl (1000 mL). The aqueous phase was extractedwith EtOAc (800 ml×3). The combined organic phase was washed withsaturated brine (800 mL), dried with anhydrous Na₂SO₄, filtered andconcentrated in vacuum. The residue was purified by silica gelchromatography (PE/EtOAc=10:1→5:1→1:4) to afford5-bromo-3-(diethoxymethyl)-1H-pyrazolo[3,4-c]pyridine (XV) (67.0 g,223.22 mmol, 49.4% yield) as yellow solid. ¹H NMR (CDCl₃, 400 MHz) δ ppm1.30 (t, J=7.03 Hz, 6H), 3.60-3.86 (m, 4H), 5.98 (s, 1H), 8.12 (d,J=1.13 Hz, 1H), 8.96 (s, 1H), 11.82 (brs, 1H); ESIMS found forC₁₁H₁₄BrN₃O₂ m/z 300.0 (M+H).

Step 4

To a solution of 5-bromo-3-(diethoxymethyl)-1H-pyrazolo[3,4-c]pyridine(XV) (20.0 g, 66.63 mmol, 1.0 eq) in CH₃CN (100 mL) was added Boc₂O(21.81 g, 99.95 mmol, 1.5 eq), DMAP (814.06 mg, 6.66 mmol, 0.10 eq) andTEA (13.49 g, 133.27 mmol, 2.0 eq) at room temperature. The mixture wasstirred at 15° C. for 1 hr. TLC (PE:EtOAc=5:1) showed that starting thematerial was consumed completely. The mixture was added water (50 mL)and extracted with EtOAc (40 mL×2). The organic layers were washed withbrine (60 mL) and concentrated under vacuum. The residue was purified bychromatography on silica gel (PE:EtOAc=10:1) to produce tert-butyl5-bromo-3-(diethoxymethyl)-1H-pyrazolo[3,4-c]pyridine-1-carboxylate(XVI) (23.70 g, 59.21 mmol, 88.9% yield) as a light yellow oil. ¹H NMR(CDCl₃, 400 MHz) δ ppm 1.29 (t, J=6.8 Hz, 6H), 1.75 (s, 9H), 3.60-3.71(m, 2H), 3.75-3.87 (m, 2H), 5.79 (s, 1H), 8.14 (d, J=1.00 Hz, 1H), 9.25(s, 1H); ESIMS found for C₁₆H₂₂BrN₃O₄ m/z 400.0 (M+H).

Preparation of THP protected intermediate (XVIII) is depicted below inScheme 3.

Step 1

To a mixture of 5-bromo-3-(dimethoxymethyl)-1H-pyrazolo[3,4-c]pyridine(XVII) (26.0 g, 69.85 mmol, 1.0 eq) and 3,4-dihydro-2H-pyran (14.69 g,174.63 mmol, 2.5 eq) in toluene (100 mL) was added4-methylbenzenesulfonic acid (2.41 g, 13.97 mmol, 0.20 eq) in oneportion at room temperature under N₂. The mixture was heated to 90° C.and stirred for 2 hr. LC/MS showed the reaction was completed. themixture was extracted with EtOAc (100 mL×3), washed with water (50 mL×2)and brine (50 mL×2). The organic layer was dried and concentrated togive a residue. the residue was purified by a column(PE:EtOAc=10:1→8:1→5:1) to give5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine-3-carbaldehyde(XVIII) (8.50 g, 30.65 mmol, 43.9% yield). ¹H NMR (CDCl₃, 500 MHz) δ ppm1.68-1.80 (m, 2H), 1.80-1.91 (m, 1H), 2.08-2.27 (m, 2H), 2.41-2.56 (m,1H), 3.77-3.88 (m, 1H), 3.90-4.00 (m, 1H), 5.93 (dd, J=2.8 Hz, J=8 Hz,1H), 8.31 (s, 1H), 9.01 (s, 1H), 10.24 (s, 1H); ESIMS found C₁₂H₁₂BrN₃O₂m/z 310.1 (M+H).

Preparation of intermediate N-(5-bromopyridin-3-yl)pivalamide (XXI) isdepicted below in Scheme 4.

Step 1

To a solution of 3-amino-5-bromo pyridine (XIX) (1.0 g, 5.78 mmol) indry pyridine (10 mL) was added pivaloyl chloride (XX) (769 mg, 6.38mmol). The reaction mixture was stirred at room temperature for 3 h. Thereaction was poured into an ice water/saturated aqueous NaHCO₃ mixtureand stirred for 30 min. The precipitate was filtered, washed with coldwater and dried at room temperature to yieldN-(5-bromopyridin-3-yl)pivalamide (XXI) as an off-white solid (1.082 g,4.22 mmol, 73.1% yield). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 1.23 (s, 9H),8.37 (d, J=2 Hz, 1H), 8.39 (t, J=2 Hz, 1H), 8.80 (d, J=2 Hz, 1H), 9.58(brs, 1H); ESIMS found C₁₀H₁₃BrN₂O m/z 258.9 (Br⁸¹M+H).

The following intermediates were prepared in accordance with theprocedure described in the above Scheme 4.

N-(5-Bromopyridin-3-yl)isobutyramide (XXII): Off-white solid, (71%yield). ¹H NMR (CDCl₃) δ ppm 8.55-8.35 (m, 3H), 7.32 (s, 1H), 2.59-2.48(m, 1H), 1.28-1.27 (d, 6H); ESIMS found C₉H₁₁BrN₂O m/z 242.9 (Br⁷⁹M+H).

N-(5-Bromopyridin-3-yl)propionamide (XXIII): Off white solid (92%yield). ¹H NMR (DMSO-d₆) δ ppm 1.09 (t, J=7.54 Hz, 3H), 2.36 (q, J=7.54Hz, 2H), 8.36 (m, 2H), 8.65 (d, J=2.07 Hz, 1H), 10.26 (s, 1H); ESIMSfound C₈H₉BrN₂O m/z 231.1 (Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)butyramide (XXIV): Yellow solid (2.1 g, 8.64mmol, 88.8% yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm 1.02 (t, J=7.2 Hz,3H), 1.74 (sxt, J=7.2 Hz, 2H), 2.40 (t, J=7.2 Hz, 2H), 8.35 (d, J=2 Hz,1H), 8.46 (t, J=2 Hz, 1H), 8.63 (d, J=2 Hz, 1H); ESIMS found C₉H₁₁BrN₂Om/z 243.1 (Br⁷⁹M+H).

N-(5-Bromopyridin-3-yl)pentanamide (XXV): Yellow solid (2.0 g, 7.78mmol, 85.3% yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm 0.98 (t, J=7.4 Hz,3H), 1.43 (sxt, J=7.4 Hz, 2H), 1.70 (quin, J=7.4 Hz, 2H), 2.43 (t, J=7.6Hz, 2H), 8.35 (s, 1H), 8.45 (d, J=2 Hz, 1H), 8.64 (d, J=2 Hz, 1H); ESIMSfound C₁₀H₁₃BrN₂O m/z 256.9 (Br⁷⁹M+H).

N-(5-Bromopyridin-3-yl)-3-methylbutanamide (XXVI): Off white solid, (67%yield), ¹H NMR (CDCl₃, 500 MHz) δ ppm 8.55-8.42 (m, 3H), 7.62 (s, 1H),2.31-2.18 (m, 3H), 1.02-1.01 (d, J=6 Hz, 6H); ESIMS found C₁₀H₁₃BrN₂Om/z 258.9 (Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)-3,3-dimethylbutanamide (XXVII): Yellow solid(1.7 g, 6.27 mmol, 78.6% yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm 1.10 (s,9H), 2.29 (s, 2H), 8.36 (d, J=1.6 Hz, 1H), 8.46 (d, J=2.0 Hz, 1H), 8.64(d, J=2.0 Hz, 1H); ESIMS found C₁₁H₁₅BrN₂O m/z 273.1 ((Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)-2-phenylacetamide (XXVIII): White solid (2.5 g,8.59 mmol, 77.9% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 3.76 (s, 2H),7.26-7.45 (m, 5H), 7.57 (brs, 1H), 8.33 (s, 1H), 8.37 (s, 2H); ESIMSfound C₁₃H₁₁BrN₂O m/z 292.8 (Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)benzamide (XXIX): White solid (2.7 g, 9.74 mmol,60% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 7.40-7.52 (m, 2H), 7.52-7.62(m, 1H), 7.86 (d, J=7.2 Hz, 2H), 8.39 (d, J=1.6 Hz, 1H), 8.46 (s, 1H),8.55 (d, J=1.6 Hz, 1H), 8.57 (d, J=2.0 Hz, 1H); ESIMS found C₁₂H₉BrN₂Om/z 278.8 (Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)cyclopropanecarboxamide (XXX): Off-white solid,(83% yield), ¹H NMR (CDCl₃, 500 MHz) δ ppm 8.46-8.39 (m, 3H), 7.54 (bs,1H), 1.56-1.50 (m, 1H), 1.13-1.07 (m, 2H), 0.96-0.90 (m, 2H); ESIMSfound for C₉H₉BrN₂O m/z 240.9 (Br⁷⁹M+H).

N-(5-Bromopyridin-3-yl)cyclobutanecarboxamide (XXXI): Yellow solid (2.1g, 6.27 mmol, 86.6% yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm 1.80-1.99 (m,1H), 1.99-2.15 (m, 1H), 2.16-2.30 (m, 2H), 2.30-2.45 (m, 2H), 3.25-3.35(m, 1H), 8.34 (d, J=2.0 Hz, 1H), 8.47 (s, 1H), 8.64 (d, J=2.0 Hz, 1H);ESIMS found C₁₀H₁₁BrN₂O m/z 257.1 (Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)cyclopentanecarboxamide (XXXII): Yellow solid(1.9 g, 7.06 mmol, 80.2% yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm 1.57-1.74(m, 2H), 1.74-1.91 (m, 4H), 1.91-2.07 (m, 2H), 2.77-2.92 (m, 1H), 8.34(d, J=1.6 Hz, 1H), 8.45 (s, 1H), 8.65 (d, J=2.0 Hz, 1H); ESIMS foundC₁₁H₁₃BrN₂O m/z 271.1 (Br⁸¹M+H).

N-(5-bromopyridin-3-yl)cyclohexanecarboxamide (XXXIII): Yellow solid(2.0 g, 7.06 mmol, 84.3% yield). ¹H NMR (CD₃OD, 400 MHz) δ ppm 1.19-1.46(m, 3H), 1.46-1.63 (m, 2H), 1.74 (d, J=11.6 Hz, 1H), 1.88 (t, J=14.0 Hz,4H), 2.40 (tt, J=11.6 Hz, J=3.6 Hz, 1H), 8.34 (d, J=2.0 Hz, 1H), 8.44(t, J=2.0 Hz, 1H), 8.64 (d, J=2.0 Hz, 1H); ESIMS found C₁₂H₁₅BrN₂O m/z285.1 (Br⁸¹M+H).

N-(5-bromopyridin-3-yl)-2-cyclohexylacetamide (XXXIV): Yellow solid (261mg, 0.878 mmol, 84.4% yield). ESIMS found C₁₃H₁₇BrN₂O m/z 297.1(Br⁸¹M+H).

Preparation of intermediate 5-bromo-N,N-dimethylpyridin-3-amine (XXXVI)is depicted below in Scheme 5.

Step 1

To a solution of 3,5-dibromopyridine (XXXV) (2.37 g, 10.0 mmol) in dryDMF (20.0 mL) was added K₂CO₃ (4.5 g, 33 mmol) and dimethylaminohydrochloride (1.79 g, 22 mmol). The mixture was heated overnight at200° C. in a sealed tube. The solution was cooled to room temperatureand excess DMF was removed under vacuum. The residue was partitionedbetween EtOAc and water. The organic phase was separated. The aqueousphase was washed with EtOAc and the combined organic phases were driedover MgSO₄, and concentrated to afford5-bromo-N,N-dimethylpyridin-3-amine (XXXVI) as an off-white solid (1.78g, 8.85 mmol, 88% yield). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 2.94 (s, 6H),7.25 (t, J=2 Hz, 1H), 7.91 (d, J=2 Hz, 1H), 8.07 (d, J=2 Hz, 1H); ESIMSfound C₇H₉BrN₂ m/z 201.1 (M+H).

Preparation of intermediate 5-bromo-N-isopropylpyridin-3-amine (XXXVII)is depicted below in Scheme 6.

Steps 1

To a solution of 5-bromopyridin-3-amine (XIX) (535 mg, 3.09 mmol) inMeOH (62 mL) was added acetone (296 μL, 4.02 mL). The pH was adjusted to4 using HOAc and stirred for 30 min. NaCNBH₃ (272 mg, 4.33 mmol) wasadded and stirred at room temperature overnight. The MeOH was removedunder vacuum and the residue was partitioned between EtOAc and saturatedaqueous NaHCO₃. The organic layer was dried over MgSO₄ and evaporatedunder vacuum. The crude product was purified on a silica gel column(100% hexane→90:10 hexane:EtOAc) to produce5-bromo-N-isopropylpyridin-3-amine (XXXVII) as an oil which slowlysolidified into an off-white solid (309 mg, 1.44 mmol, 47% yield). ¹HNMR (DMSO-d₆, 500 MHz) δ ppm 1.12 (d, J=6.3 Hz, 6H), 3.55-3.59 (m, 1H),6.03 (d, J=7.9 Hz, 1H), 7.05-7.06 (m, 1H), 7.75 (d, J=2 Hz, 1H), 7.90(d, J=2 Hz, 1H); ESIMS found C₈H₁₁BrN₂ m/z 215.1 (M+H).

Preparation of intermediate1-(5-bromopyridin-3-yl)-N,N-dimethylmethanamine (XXXIX) is depictedbelow in Scheme 7.

Steps 1

Preparation of 1-(5-bromopyridin-3-yl)-N,N-dimethylmethanamine (XXXIX)was performed following the procedure listed in Scheme 6, Step 1. Brownoil (1.20 g, 5.59 mmol, 45% yield). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 2.15(s, 6H), 3.43 (s, 2H), 7.94 (s, 1H), 8.47 (d, J=1.1 Hz, 1H), 8.59 (d,J=2.2 Hz, 1H); ESIMS found C₈H₁₁BrN₂ m/z 215 (M^(Br79)+H) and 217(M^(Br81)+H).

Preparation of intermediate3-bromo-5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridine (XL) is depictedbelow in Scheme 8.

Steps 1

To a mixture of 5-bromopyridine-3-carbaldehyde (XXXVIII) (6.00 g, 32.26mmol, 1.0 eq), 3,3-difluoropyrrolidine (5.56 g, 38.71 mmol, 1.20 eq) andTEA (5.39 mL, 38.71 mmol, 1.2 Eq) in DCE (200 mL) was stirred at roomtemperature for 30 min, then added sodium triacetoxyborohydride (10.25g, 48.38 mmol, 1.50 eq) in one portion at room temperature under N₂. Themixture was stirred at room temperature for 6 hours. TLC showed thereaction was complete. The reaction was quenched with 1N NaOH (100 mL),extracted with DCE (100 mL×2). The combined organic layers were washedwith brine (100 mL), dried and concentrated. The residue was purified bysilica gel chromatography (column height: 50 mm, diameter: 50 mm,300-400 mesh silica gel, DCM/MeOH=30/1→20/1) to give3-bromo-5-((3,3-difluoropyrrolidin-1-yl)methyl) pyridine (XL): Yellowoil (8.00 g, 28.9 mmol, 89.5% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 2.30(spt, J=7.2 Hz. 2H), 2.75 (t, J=6.8 Hz, 2H), 2.91 (t, J=13.2 Hz, 2H),7.85 (s, 1H), 8.45 (s, 1H), 8.59 (d, J=2 Hz, 1H); ESIMS found forC₁₀H₁₁BrF₂N₂ m/z 277.0 (M+H).

The following intermediates were prepared in accordance with theprocedure described in the above Scheme 7 or Scheme 8.

3-Bromo-5-(pyrrolidin-1-ylmethyl)pyridine (XLI): Golden liquid (1.35 g,97% yield). ¹H NMR (DMSO-d₆) 1.68-1.71 (m, 4H), 2.42-2.44 (m, 4H), 3.60(s, 2H), 7.96 (s, 1H), 8.48 (d, J=2 Hz, 1H), 8.58 (d, J=3 Hz, 1H); ESIMSfound for C₁₀H₁₃BrN₂ m/z 242.2 (M+H).

3-Bromo-5-(piperidin-1-ylmethyl)pyridine (XLII): Brown liquid (13.1 g,94% yield). ¹H NMR (DMSO-d₆) 1.36-1.39 (m, 2H), 1.46-1.51 (m, 4H),2.31-2.32 (m, 4H), 3.46 (s, 2H), 7.94 (s, 1H), 8.47 (d, J=2 Hz, 1H),8.58 (d, J=3 Hz, 1H); ESIMS found for C₁₁H₁₅BrN₂ m/z 257.0 (M+H).

N-((5-Bromopyridin-3-yl)methyl)ethanamine (XLIII): Golden liquid (1.29g, 6.00 mmol, 60% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 1.14 (t, J=7.2Hz, 3H), 2.67 (q, J=7.2 Hz, 2H), 3.79 (s, 2H), 7.85 (t, J=2 Hz, 1H),8.46 (d, J=1.6 Hz, 1H), 8.56 (d, J=2.4 Hz, 1H); ESIMS found forC₈H₁₁BrN₂ m/z 215.1 (M+H).

N-Benzyl-1-(5-bromopyridin-3-yl)methanamine (XLIV): Yellow oil (8.0 g,28.9 mmol, 89.5% yield). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 3.71 (s, 2H),3.74 (s, 2H), 7.18-7.28 (m, 1H), 7.28-7.40 (m, 4H), 8.04 (s, 1H), 8.52(s, 1H), 8.58 (s, 1H); ESIMS found for C₁₃H₁₃BrN₂ m/z 277.1 (M+H).

Preparation of intermediate tert-butyl (5-bromopyridin-3-yl)methyl(cyclopentylmethyl)carbamate (XLIX) is depicted below in Scheme 9.

Step 1

To a solution of 5-bromonicotinaldehyde (XXXVIII) (2.0 g, 10.8 mmol, 1eq) in MeOH (20 mL) was added NaBH₄ (2.4 g, 64.9 mmol, 6 eq) and thereaction mixture was stirred at room temperature for 3 h. The mixturewas concentrated in vacuo and the residue was diluted in water (15 mL),the aqueous phase was extracted with DCM (10 mL×3). The combined organiclayers were dried over MgSO₄, filtered and concentrated in vacuo toafford (5-bromopyridin-3-yl)methanol (XLV) (1.8 g, 9.57 mmol, 90.0%yield) as a colorless oil. ¹H NMR (CDCl₃, 500 MHz) δ ppm 4.73 (s, 2H),7.90 (s, 1H), 8.47 (s, 1H), 8.57 (s, 1H). ESIMS found for C₆H₆BrNO m/z188.0 (M+H).

Step 2

To a stirred solution of (5-bromopyridin-3-yl)methanol (XLV) (1.60 g,8.5 mmol, 1 eq), phthalimide (1.24 g, 8.5 mmol, 1 eq) and PPh₃ (3.33 g,12.75 mmol, 1.5 eq) in anhydrous THF (15 mL) was added DEAD (2.21 g,12.75 mmol, 1.5 eq) dropwise at 0° C. under N₂. Then the reactionmixture was stirred at room temperature for 6 h. The mixture was washedwith saturated NaHCO₃ solution (15 mL), water (15 mL) and brine (15 mL)subsequently. The organic layers were dried over MgSO₄, concentratedunder reduced pressure, the resultant residue was purified by flashchromatography on silica gel (PE:EtOAc=4:1) to give2-((5-bromopyridin-3-yl)methyl)isoindoline-1,3-dione (XLVI) (2.5 g, 7.88mmol, 82.3% yield) as a white solid. ESIMS found for C₁₄H₉BrN₂O₂ m/z317.1 (M+H).

Step 3

A solution of 2-((5-bromopyridin-3-yl)methyl)isoindoline-1,3-dione(XLVI) (1.9 g, 6.0 mmol, 1 eq) and hydrazine hydrate (2.0 g, 40 mmol, 6eq) in EtOH (20 mL) was heated at 70° C. for 3 h. The mixture wasfiltered through a Celite® pad and the filtrate was concentrated invacuo, the crude product was dissolved in 1N HCl solution (15 mL) andconcentrated to dryness, then it was washed with acetone (10 ml×3), theprecipitate was collected by filtration, dried in vacuo to give(5-bromopyridin-3-yl)methanamine (XLVII) (1.3 g, 6.95 mmol, 97.7% yield)as a white solid. ¹H NMR (D₂O, 500 MHz) δ ppm 4.34 (s, 2H), 8.56 (s,1H), 8.75 (d, J=1.2 Hz, 1H), 8.91 (d, J=1.6 Hz, 1H). ESIMS found forC₆H₇BrN₂ m/z 187.0 (M+H).

Step 4

A solution of (5-bromopyridin-3-yl)methanamine (XLVII) (1.30 g, 5.8mmol, 1.0 eq), cyclopentanecarbaldehyde (0.57 g, 5.8 mmol, 1.0 eq) andTEA (0.60 g, 5.8 mmol, 1.0 eq) in MeOH (15 mL) was stirred at roomtemperature for 2 h. Then NaBH₃CN (1.98 g, 34.6 mmol, 6.0 eq) was addedand the mixture was stirred at the same temperature for another 3 h. Thesolvent was removed under reduced pressure and the residue was dilutedin water (20 mL) and extracted with DCM (10 mL×3), combined organiclayers were dried over MgSO₄ and concentrated in vacuo to give1-(5-bromopyridin-3-yl)-N-(cyclopentylmethyl)methanamine (XLVIII) (1.23g, 4.57 mmol, 79.3% yield) as a yellow oil. ¹H NMR (CDCl₃, 400 MHz) δppm 1.07-1.23 (m, 2H), 1.47-1.67 (m, 4H), 1.70-1.84 (m, 2H), 2.02 (spt,J=7.6 Hz. 1H), 2.53 (d, J=7.2 Hz, 2H), 3.80 (s, 2H), 7.86 (s, 1H), 8.47(s, 1H), 8.56 (d, J=2.0 Hz, 1H); ESIMS found for C₁₂H₁₇BrN₂ m/z 269.1(M+H).

Step 5

To a solution of 1-(5-bromopyridin-3-yl)-N-(cyclopentylmethyl)methanamine (XLVIII) (1.00 g, 3.7 mmol, 1 eq) and TEA (0.93 g, 9.2 mmol,2.5 eq) in DCM (20 mL) was added portionwise (Boc)₂O (0.85 g, 4.0 mmol,1.1 eq) at 0° C., the reaction mixture was stirred at room temperaturefor 1 h. The mixture was washed with water (10 mL), brine (10 mL), theorganic layer was separated, dried over MgSO₄ and concentrated in vacuoto give tert-butyl (5-bromopyridin-3-yl)methyl(cyclopentylmethyl)carbamate (XLIX) (1.25 g, 3.38 mmol, 91.9% yield) asa white solid. ESIMS found for C₁₇H₂₅BrN₂O₂ m/z 369.1 (M+H).

Preparation of intermediate 3-bromo-5-(cyclohexyloxy)pyridine (LII) isdepicted below in Scheme 10.

Step 1

To a solution of 5-bromopyridin-3-ol (L) (523 mg, 3.01 mmol) in THF (30mL) cooled to 0° C. were added triphenylphosphine (867 mg, 3.31 mmol)and cyclohexanol (LI) (331 mg, 3.31 mmol) followed by(E)-bis(4-chlorobenzyl) diazene-1,2-dicarboxylate (1.21 g, 3.31 mmol),added portionwise. The reaction mixture was then stirred at 25° C.overnight. The reaction was worked-up with a EtOAc-NaHCO₃ extraction andthe solid filtered off. The solvent was removed and the residue waspurified by Isco (20% EtOAc-Hexanes) to give3-bromo-5-(cyclohexyloxy)pyridine (LII) (209 mg, 0.82 mmol, 27.2% yield)as a yellow oil. ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 1.21-1.31 (m, 1H)1.34-1.48 (m, 4H) 1.49-1.57 (m, 1H) 1.70 (br dd, J=9.74, 4.25 Hz, 2H)1.88-1.96 (m, 2H) 2.50 (dt, J=3.70, 1.72 Hz, 5H) 4.46-4.54 (m, 1H) 7.72(t, J=2.20 Hz, 1H) 8.24 (d, J=1.92 Hz, 1H) 8.27 (d, J=2.47 Hz, 1H).

The following intermediate was prepared in accordance with the proceduredescribed in the above Scheme 10.

tert-Butyl 4-((5-bromopyridin-3-yl)oxy)piperidine-1-carboxylate (LIII):Yellow oil (244 mg, 0.683 mmol, 23.2% yield). ESIMS found forC₁₅H₂₁BrN₂O₃ m/z 358.3 (M+H).

Preparation of intermediate 3-(benzyloxy)-5-bromopyridine (LV) isdepicted below in Scheme 11.

Step 1

To a solution of 5-bromopyridin-3-ol (L) (174 mg, 1.0 mmol) in DMF (3mL) was added potassium carbonate (415 mg, 3.0 mmol). The slurry washeated at 90° C. for 1 hour and then cooled to 25° C. The(bromomethyl)benzene (LIV) (171 mg, 1.0 mmol) was added and the mixturewas stirred at 25° C. overnight. The reaction was worked-up using asaturated sodium bicarbonate and ethyl acetate extraction. The productwas purified by ISCO column eluted with 40-100% EtOAc-Hexanes. The3-(benzyloxy)-5-bromopyridine (LV) (105 mg, 0.398 mmol, 39.8% yield) wasobtained as yellow oil. MS: 266.1. ESIMS found for C₁₂H₁₀BrNO m/z 266.1(M+H).

The following intermediates were prepared in accordance with theprocedure described in the above Scheme 11.

3-Bomo-5-(2-(pyrrolidin-1-yl)ethoxy)pyridine (LVI): Yellow oil ((97 mg,0.358 mmol, 15.56% yield). ESIMS found for C₁₁H₁₅BrN₂O m/z 272.2 (M+H).

2-((5-bromopyridin-3-yl)oxy)-N,N-dimethylethan-1-amine (LVII): Yellowoil (97 mg, 0.396 mmol, 28.9% yield). ESIMS found for C₉H₁₃BrN₂O m/z245.1 (M+H).

1-(2-(3-bromo-5-fluorophenoxy)ethyl)pyrrolidine (LVIII): Yellow oil (370mg, 1.284 mmol, 85.8% yield). ESIMS found for C₁₂H₁₅BrFNO m/z 289.0(M+H).

2-(3-bromo-5-fluorophenoxy)-N,N-dimethylethan-1-amine (LIX): Yellow oil(364 mg, 1.389 mmol, 50.2% yield). ESIMS found for C₁₀H₁₃BrFNO m/z 263.9(M+H).

Preparation of intermediate tert-butyl4-(2-((5-bromopyridin-3-yl)amino)-2-oxoethyl)piperidine-1-carboxylate(LXI) is depicted below in Scheme 12.

Step 1

To a solution of 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)acetic acid(LX) (3.4 g, 13.97 mmol) in DCM (10 mL) was added DMF (1 mL). Thesolution was cooled in ice-water to 0° C. Oxalyl chloride (1.835 mL,20.96 mmol) was then added dropwise. The mixture was stirred for onehour at 25° C. The organic volatile was then removed under vacuum. Theresidue was dissolved in DCM (10 mL). DMAP (0.171 g, 1.397 mmol) and5-bromopyridin-3-amine (XIX) (2.418 g, 13.97 mmol) were added to thesolution and cooled to 0° C. DIEA (4.88 ml, 27.9 mmol) was then addeddropwise and the mixture was stirred for 2 hours at 25° C. The reactionwas worked-up with DCM and saturated NaHCO3. The product was purified byISCO eluted with 0-100% EtOAc-Hexanes. The tert-butyl4-(2-((5-bromopyridin-3-yl)amino)-2-oxoethyl)piperidine-1-carboxylate(LXI) (2.82 g, 7.08 mmol, 50.7% yield) was obtained as yellow oil. ESIMSfound for C₁₇H₂₄BrN₃O₃ m/z 343.1 (M−56).

The following intermediate was prepared in accordance with the proceduredescribed in the above Scheme 12.

N-(5-Bromopyridin-3-yl)-2-(dimethylamino)acetamide (LXII): Yellow oil(528 mg, 2.05 mmol, 19.0% yield). ESIMS found for C₉H₁₂BrN₃O m/z 259.3(M+H).

Preparation of tert-butyl(1-(6-chloropyrazin-2-yl)azetidin-3-yl)carbamate (LXV) is depicted belowin Scheme 13.

Step 1

To a solution of tert-butyl azetidin-3-ylcarbamate hydrochloride (LXIII)(2 g, 9.58 mmol) in dry DMF (19.2 mL) was added DIPEA (8.37 ml, 47.9mmol). To this mixture was added 2,6-dichloropyrazine (LXIV) (1.428 g,9.58 mmol) and the reaction was stirred at 95° C. for 3 hours. Thereaction was quenched with water (20 mL) and extracted with EtOAc. Theorganic layer was dried over anhydrous Na₂SO₄, filtered andconcentrated. The residue was purified by silica gel columnchromatography (40 g) (100% hexanes→hexanes:EtOAc 1:1) to yieldtert-butyl (1-(6-chloropyrazin-2-yl)azetidin-3-yl)carbamate (LXV)(2.2882 g, 8.04 mmol, 84% yield) as a white solid. ESIMS found forC₁₂H₁₇ClN₄O₂ m/z 285.1 (M+H).

Preparation of intermediate 2′-fluorobiphenyl-2,3-diamine (LXIX) isdepicted below in Scheme 14.

Step 1

A solution of 3-bromo-2-nitroaniline (LXVI) (2.00 g, 9.30 mmol, 1 eq),2-fluorophenylboronic acid (LXVII) (1.42 g, 10.14 mmol, 1.1 eq),Pd(PPh₃)₄ (0.35 g, 0.03 mmol, 0.03 eq), Na₂CO₃ (1.95 g, 18.40 mmol, 2eq) in a mixed solvent of toluene (15 mL), H₂O (9 mL) and EtOH (3 ml)was stirred at 75° C. for 15 h under nitrogen atmosphere. Then thereaction mixture was washed with brine (20 mL) and dried over anhydrousNa₂SO₄, filtered and concentrated in vacuo, the resultant residue waspurified by chromatography on silica gel (PE:EtOAc=3:1) to afford2′-fluoro-2-nitrobiphenyl-3-amine (LXVIII) (1.0 g, 4.30 mmol, 46.6%yield) as a yellow solid. ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 6.54 (d, J=6.4Hz, 1H), 6.64 (s, 2H), 7.04 (dd, J=8.8 Hz, J=1.2 Hz, 1H), 7.18-7.31 (m,2H), 7.33-7.47 (m, 3H); ESIMS found for C₁₂H₉FN₂O₂ m/z 233 (M+H).

Step 2

To a solution of 2′-fluoro-2-nitrobiphenyl-3-amine (LXVIII) (1.0 g, 3.45mmol, 1 eq) in MeOH (50 mL) was added Pd/C (0.5 g) under nitrogenatmosphere, the mixture was stirred under 50 psi of H₂ for 6 h at roomtemperature. Then the mixture was filtered and concentrated in vacuo toafford 2′-fluorobiphenyl-2,3-diamine (LXIX) (0.8 g, 3.96 mmol, 92%yield) as a black solid. ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 3.99 (s, 2H),4.62 (s, 2H), 6.32 (d, J=7.6 Hz, 1H), 6.49 (t, J=7.6 Hz, 1H), 6.60 (d,J=7.6 Hz, 1H), 7.21-7.35 (m, 3H), 7.35-7.45 (m, 1H); ESIMS found forC₁₂H₁₁FN₂ m/z 203 (M+H).

The following intermediates were prepared in accordance with theprocedure described in the above Scheme 14.

3′-Fluorobiphenyl-2,3-diamine (LXX): White solid (2.0 g, 9.89 mmol, 81%yield). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 4.16 (s, 2H), 4.64 (s, 2H), 6.38(dd, J=7.6 Hz, J=1.6 Hz, 1H), 6.51 (t, J=7.6 Hz, 1H), 6.60 (d, J=6 Hz,1H), 7.11-7.26 (m, 3H), 7.48 (q, J=6.4 Hz, 1H); ESIMS found forC₁₂H₁₁FN₂ m/z 203 (M+H).

4′-Fluorobiphenyl-2,3-diamine (LXXI): White solid (2.4 g, 11.87 mmol,98% yield). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 4.07 (s, 2H), 4.60 (s, 2H),6.34 (dd, J=7.6 Hz, J=1.6 Hz, 1H), 6.50 (t, J=7.6 Hz, 1H), 6.58 (dd,J=7.6 Hz, J=1.6 Hz, 1H), 7.26 (t, J=7.6 Hz, 2H), 7.40 (q, J=5.6 Hz, 2H);ESIMS found for C₁₂H₁₁FN₂ m/z 203 (M+H).

3-(Pyridin-3-yl)benzene-1,2-diamine (LXXII): White solid (1.36 g, 7.34mmol, 92.5% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 1.57 (brs, 2H), 3.42(brs, 2H), 6.66 (dd, J=6 Hz, J=3.2 Hz, 1H), 6.68-6.72 (m, 2H), 7.31 (dd,J=8 Hz, J=4.8 Hz, 1H), 7.71 (td, J=8 Hz, J=2 Hz, 1H), 8.54 (dd, J=4.8Hz, J=1.6 Hz, 1H), 8.64 (d, J=1.6 Hz, 1H); ESIMS found for C₁₁H₁₁N₃ m/z186 (M+H).

3-(Thiophen-3-yl)benzene-1,2-diamine (LXXIII): White solid (1.2 g, 6.31mmol, mmol, 94% yield). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 4.19 (s, 2H),4.59 (s, 2H), 6.47 (dd, J=4.8 Hz, J=1 Hz, 2H), 6.55 (q, J=4.8 Hz, 1H),7.24 (dd, J=4.8 Hz, J=1 Hz, 1H), 7.50 (t, J=1.6 Hz, 1H), 7.63 (dd, J=4.8Hz, J=2.8 Hz, 1H); ESIMS found for C₁₀H₁₀N₂S m/z 191 (M+H).

3-(Furan-3-yl)benzene-1,2-diamine (LXXIV): White solid (1.3 g, 7.46mmol, mmol, 85% yield). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 4.24 (brs, 2H),4.57 (brs, 2H), 6.46-6.50 (m, 1H), 6.50-6.56 (m, 2H), 6.72 (s, 1H), 7.74(t, J=1.6 Hz, 1H), 7.87 (s, 1H); ESIMS found for C₁₀H₁₀N₂O m/z 175(M+H).

3-(Thiophen-2-yl)benzene-1,2-diamine (LXXV): Brown oil (925.5 mg, 4.86mmol, 60.9% yield). ESIMS found C₁₀H₁₀N₂S m/z 191.1 (M+H).

1-(5-(2,3-Diaminophenyl)thiophen-2-yl) ethan-1-one (LXXVI): Brown oil(530 mg, 2.28 mmol, 88.1% yield). ¹H NMR (CDCl₃, 400 MHz) δ ppm 2.59 (s,3H), 3.47 (brs, 2H), 3.86 (brs, 2H), 6.70-6.81 (m, 2H), 6.88 (dd, J=2Hz, J=7.6 Hz, 1H), 7.22 (d, J=3.6 Hz, 1H), 7.71 (d, J=4 Hz, 1H); ESIMSfound C₁₂H₁₂N₂OS m/z 233.0 (M+H).

2′,3′-Diamino-5-fluoro-[1,1′-biphenyl]-3-ol (LXXVII): Black oil (165 mg,0.756 mmol, 83.0% yield). ESIMS found for C₁₂H₁₁FN₂O m/z 219.1 (M+H).

3′-Fluoro-5′-methoxy-[1,1′-biphenyl]-2,3-diamine (LXXVIII): Black oil(187 mg, 0.805 mmol, 93.4% yield). ESIMS found for C₁₃H₁₃FN₂O m/z 233.1(M+H).

3′-Fluoro-5′-(2-(pyrrolidin-1-yl) ethoxy)-[1,1′-biphenyl]-2,3-diamine(LXXIX): Black oil (300 mg, 0.951 mmol, 68.4% yield). ESIMS found forC₁₈H₂₂FN₃O m/z 316.1 (M+H).

3′-(2-(Dimethylamino)ethoxy)-5′-fluoro-[1,1′-biphenyl]-2,3-diamine(LXXX): Black oil (267 mg, 0.923 mmol, 63.2% yield). ESIMS found forC₁₆H₂₀FN₃O m/z 290.1 (M+H).

Preparation of intermediate 3-(pyridin-4-yl)benzene-1,2-diamine (LXXXVI)is depicted below in Scheme 15.

Step 1

To a solution of 2-bromoaniline (LXXXI) (50 g, 0.29 mol, 1 eq) in aceticanhydride (265 mL) was added dropwise nitric acid (fuming) (36.75 mL,0.93 mol, 3.2 eq) at 0° C. and then stirred at that temperature, whenthe starting material was consumed, the mixture was filtered, thefiltrate was poured into ice water. The aqueous phase was basified withaqueous solution of sodium bicarbonate to pH=7, then the mixture wasextracted with EtOAc (30 mL×3). The organic layers were combined, driedand concentrated in vacuo to give the N-(2-bromo-6-nitrophenyl)acetamide(LXXXII) (12.6 g, 48.6 mmol, 16.7% yield) as a white solid. ¹H NMR(DMSO-d₆, 400 MHz) δ ppm 2.06 (s, 3H), 7.43 (t, J=8 Hz, 1H), 7.94 (d,J=8 Hz, 1H), 8.05 (d, J=8 Hz, 1H); ESIMS found for C₈H₇BrN₂O₃ m/z 259(M+H).

Step 2

A degassed mixture of N-(2-bromo-6-nitrophenyl)acetamide (LXXXII) (2.59g, 10 mmol, 1.0 eq),4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (LXXXIII) (2.05g, 10 mmol, 1.3 eq), Na₂CO₃ (2.12 g, 20 mmol, 2 eq) and Pd(PPh₃)₄ (1.16g, 1 mmol, 0.1 eq) in a mixed solvent of DME (30 mL) and H₂O (10 mL) washeated to reflux under nitrogen overnight, the mixture was poured ontowater (40 ml) and extracted with EtOAc (30 mL×3). The combined organiclayers were dried over Na₂SO₄, filtered and concentrated in vacuo,purification the resultant residue was purified by column chromatography(EtOAc:PE=1:4→100% EtOAc) to affordN-(2-nitro-6-(pyridin-4-yl)phenyl)acetamide (LXXXIV) (1.42 g, 5.52 mmol,55% yield) as a yellow solid. ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.92 (s,3H), 7.46 (d, J=5.6 Hz, 2H), 7.69 (t, J=8 Hz, 1H), 7.80 (dd, J=7.6 Hz,J=1.2 Hz, 1H), 8.06 (dd, J=8 Hz, J=1.6 Hz, 1H), 8.73 (d, J=6 Hz, 2H),9.96 (s, 1H); ESIMS found for C₁₃H₁₁N₃O₃ m/z 258 (M+H).

Step 3

To a solution of N-(2-nitro-6-(pyridin-4-yl)phenyl)acetamide (LXXXIV)(3.94 g, 15 mmol, 1 eq) in MeOH (20 mL) was added 2 N aqueous NaOHsolution (50 mL) and the mixture was refluxed until the startingmaterial was consumed completely, the precipitate was collected byfiltration to afford the 2-nitro-6-(pyridin-4-yl)aniline (LXXXV) (3.0 g,13.9 mmol, 91% yield) as yellow solid. ESIMS found for C₁₁H₉N₃O₂ m/z 216(M+H).

Step 4

To a solution of 2-nitro-6-(pyridin-4-yl)aniline (LXXXV) (3 g, 14 mmol,1 eq) in EtOAc (350 mL) was added Pd/C (0.3 g) and the mixture wasstirred at room temperature under 1 atm of H₂ atmosphere overnight, themixture was filtered and concentrated in vacuo to give the product3-(pyridin-4-yl)benzene-1,2-diamine (LXXXVI) (2.4 g, 13.0 mmol, 93%yield) as a white solid. ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 4.35 (s, 2H),4.75 (s, 2H), 6.45 (dd, J=7.6 Hz, J=1 Hz, 1H), 6.58 (t, J=7.6 Hz, 1H),6.67 (d, J=6.8 Hz, 1H), 7.47 (d, J=6 Hz, 2H), 8.65 (d, J=6 Hz, 2H);ESIMS found for C₁₁H₁₁N₃ m/z 186 (M+H).

Preparation of intermediate 3-(pyridin-2-yl)benzene-1,2-diamine 3HCl(XCI) is depicted below in Scheme 16.

Step 1

To a solution of 2-bromopyridine (LXXXVII) (10 g, 63 mmol, 1.00 eq) inTHF (150 mL) was added n-BuLi (25.3 mL, 63 mmol, 1.00 eq) and themixture was stirred at −70° C. for 30 min under nitrogen atmosphere.Then n-Bu₃SnCl (21.7 g, 67 mmol, 1.06 eq) was added and the mixture wasstirred at the same temperature for another 2 h. Saturated ammoniumchloride solution (150 mL) was added to the solution and extracted withEtOAc (150 mL×3). The combined organic layers were dried over Na₂SO₄,filtered and concentrated in vacuo to afford the crude2-(tributylstannyl)pyridine (LXXXVIII) (25.9 g, 63 mmol, 100% yield) asa yellow oil. The crude product was used without further purification.

Step 2

A degassed mixture of N-(2-bromo-6-nitrophenyl)acetamide (DOOM) (4.8 g,19 mmol, 1.00 eq), 2-(tributylstannyl)pyridine (LXXXVIII) (7.5 g, 20mmol, 1.05 eq) and Pd(PPh₃)₄ (2.1 g, 1.8 mmol, 0.01 eq) in toluene (60mL) was heated to reflux under nitrogen overnight. Saturated sodiumbicarbonate solution (50 mL) was then added to the mixture and it wasextracted with EtOAc (50 mL×3). The combined organic layers were driedover Na₂SO₄, filtered and concentrated in vacuo, the residue waspurified by column chromatography on silica gel (EtOAc:PE=1:2→100%EtOAc) to afford N-(2-nitro-6-(pyridin-2-yl)phenyl)acetamide (LXXXIX)(4.4 g, 17.1 mmol, 92% yield) as a white-off solid. ¹H NMR (DMSO-d₆, 400MHz) δ ppm 1.93 (s, 3H), 7.43-7.51 (m, 1H), 7.51-7.65 (m, 1H), 7.67 (d,J=7.6 Hz, 1H), 7.97 (dd, J=7.6 Hz, J=2.4 Hz, 3H), 8.75 (d, J=4.4 Hz,1H), 10.52 (s, 1H); ESIMS found for C₁₃H₁₁N₃O₃ m/z 258.1 (M+H).

Step 3

To a solution of N-(2-nitro-6-(pyridin-2-yl)phenyl)acetamide (LXXXIX)(4.41 g, 17 mmol, 1 eq) in MeOH (20 mL) was added 2N NaOH aqueous (50mL) and the mixture was refluxed until the stirring material wasconsumed completely. The mixture was concentrated in vacuo to remove theMeOH and the precipitate was collected by filtration to afford2-nitro-6-(pyridin-2-yl)aniline (XC) (2.4 g, 11.2 mmol, 65% yield) as ayellow solid. ESIMS found for C₁₁H₉N₃O₂ m/z 216.1 (M+H).

Step 4

To a solution of 2-nitro-6-(pyridin-2-yl)aniline (XC) (2.4 g, 0.01 mmol,1 eq) in EtOAc (350 mL) was added Pd/C (1 g) and the mixture was stirredat room temperature under 1 atm of H₂ atmosphere overnight, filtered andthen concentrated in vacuo, to give 3-(pyridin-2-yl)benzene-1,2-diamine(1.9 g, 10.3 mmol, 89% yield) as a yellow oil. ESIMS found for C₁₁H₁₁N₃m/z 186.0 (M+H).

Step 5

To a solution of 3-(pyridin-2-yl)benzene-1,2-diamine (1.86 g, 0.01 mmol)in EtOAc (200 mL) was added HCl in EtOAc (40 mL) and the mixture wasstirred at 0° C. for 20 min. The precipitate was collected by filtrationto give 3-(pyridin-2-yl)benzene-1,2-diamine-3HCl (XCI) as a yellowsolid. ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 6.89 (t, J=7.6 Hz, 1H), 7.33(brs, 1H), 7.51 (d, J=7.2 Hz, 1H), 7.54-7.66 (m, 2H), 7.97 (d, J=8 Hz,1H), 8.16 (brs, 1H), 8.75 (brs, 1H).

Preparation of intermediate 3-(piperidin-1-yl)benzene-1,2-diamine (XCIV)is depicted below in Scheme 17.

Step 1

To a solution of 3-chloro-2-nitroaniline (XCII) (2.00 g, 11.6 mmol, 1eq) and piperidine (2.95 g, 34.7 mmol, 3 eq) in DMF (60 ml) was addedK₂CO₃ (4.78 g, 34.4 mmol, 3 eq) in one portion and the mixture wasstirred at 120° C. under nitrogen overnight. The reaction mixture wasdiluted with EtOAc (60 ml) and washed with saturated NaHCO₃ solution (50mL). The organic phases were dried over Na₂SO₄ and concentrated invacuo, the resultant residue was purified by silica gel columnchromatography (PE:EtOAc=5:1→1:1) to give2-nitro-3-(piperidin-1-yl)aniline (XCIII) (1.8 g, 8.14 mmol, 70.3%yield) as a black solid. ESIMS found for C₁₁H₁₅N₃O₂ m/z 222 (M+H).

Step 2

A mixture of 2-nitro-3-(piperidin-1-yl)aniline (XCIII) (1.64 g, 6.9mmol, 1 eq) and Pd/C (0.50 g) in MeOH (20 mL) was stirred at roomtemperature under 30 psi H₂ overnight. After the starting material wasconsumed completely, the mixture was filtered through a Celite pad andthe filtrate was concentrated in vacuo to give the3-(piperidin-1-yl)benzene-1,2-diamine (XCIV) (1.1 g, 5.75 mmol, 76%yield) as a yellow solid. ¹H NMR (CDCl₃, 400 MHz) δ ppm 1.59 (brs, 2H),1.73 (quin, J=5.6 Hz, 4H), 2.84 (brs, 4H), 3.50 (brs, 4H), 6.52 (dd,J=6.4 Hz, J=1.6 Hz, 1H), 6.59-6.75 (m, 2H); ESIMS found for C₁₁H₁₇N₃ m/z192 (M+H).

Preparation of intermediate3-(4-methyl-imidazol-1-yl)-benzene-1,2-diamine (XCVI) is depicted belowin Scheme 18.

Step 1

A solution of 3-chloro-2-nitro-aniline (XCII) (1.0 g, 5.8 mmol),potassium carbonate (2.4 g, 17.4 mmol), and 4-methylimidazole in dry DMFwas heated overnight at 120° C. under nitrogen. The reaction was cooledand the solvent was evaporated in vacuo. The residue was suspended in asaturated NaHCO₃ solution and extracted with CH₂Cl₂. The combinedorganic phases were dried over MgSO₄ and concentrated in vacuo. Thecrude product was purified by flash chromatography to provide3-(4-methyl-imidazol-1-yl)-2-nitro-phenylamine (XCV). ¹H NMR (CDCl₃, 400MHz) δ ppm 2.19 (s, 3H), 6.53 (m, 1H), 6.79 (m, 1H), 6.93 (m, 1H), 7.32(m, 1H), 7.60 (m, 1H).

Step 2

To a solution of 3-(4-methyl-imidazol-1-yl)-2-nitro-phenylamine (XCV) inMeOH was added with 5% Pd/C. The combination was stirred under ahydrogen filled balloon at 40° C. for 6 h. The solution was thenfiltered through a pad of Celite. The filtrate was concentrated in vacuoto get 3-(4-methyl-imidazol-1-yl)-benzene-1,2-diamine (XCVI). ¹H NMR(CDCl₃, 400 MHz) δ ppm 2.17 (s, 3H), 6.54 (m, 1H), 6.80 (m, 1H), 6.97(m, 1H), 7.28 (m, 1H), 7.56 (m, 1H).

Preparation of intermediate (XCIX) is depicted below in Scheme 19.

Step 1

A mixture of 1-methylpiperazine (XCVII) (20 mL) and3-chloro-2-nitroaniline (XCII) (1.5 g, 8.7 mmol, 1 eq) was stirred at50° C. for 1 h under microwave irradiation. The reaction mixture wasdiluted with water (100 mL) and filtered, the cake washed with water (30mL×3), dried in vacuo to give the3-(4-methylpiperazin-1-yl)-2-nitroaniline (XCVIII) (1.64 g, 6.94 mmol,80% yield) as a yellow solid. ESIMS found for C₁₁H₁₆N₄O₂ m/z 237 (M+H).

Step 2

A mixture of 3-(4-methylpiperazin-1-yl)-2-nitroaniline (XCVIII) (1.64 g,6.9 mmol, 1 eq) and Pd/C (0.2 g) in MeOH (20 mL) was stirred under 30psi of H₂ at room temperature overnight. The reaction was monitored byTLC. The mixture was filtered and the filtrate was concentrated in vacuoto give the 3-(4-methylpiperazin-1-yl)benzene-1,2-diamine (XCIX) (1.31g, 6.35 mmol, 92% yield) as a black solid. ¹H NMR (CDCl₃, 400 MHz) δ ppm2.30 (s, 3H), 3.30 (brs, 2H), 3.68 (brs, 2H), 6.46 (dd, J=7.2 Hz, J=2Hz, 1H), 6.54-6.63 (m, 2H); ESIMS found for C₁₁H₁₈N₄ m/z 207 (M+H).

Preparation of intermediate 3-(5-fluorothiophen-2-yl)benzene-1,2-diamine(CIII) is depicted below in Scheme 20.

Step 1

A solution of 2-bromo-6-nitroaniline (C) (800 mg, 3.67 mmol, 1.0 eq),2-(5-fluorothiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (CI)(1.0 g, 4.4 mmol, 1.2 eq), Pd(dppf)Cl₂ (268 mg, 0.37 mmol, 0.10 eq) andCs₂CO₃ (2.39 g, 7.34 mmol, 2.0 eq) in dioxane (20 mL) and H₂O (4 mL) wasde-gassed and then heated to 100° C. under N₂ for 3 h. TLC(PE:EtOAc=1:1) showed the starting material was consumed completely. Themixture was concentrated in vacuum to give a residue, which was purifiedby column chromatography (PE:EtOAc=10:1) to afford the2-(5-fluorothiophen-2-yl)-6-nitroaniline (CII) (540 mg, 2.27 mmol, 61.7%yield). ESIMS found for C₁₀H₇FN₂O₂S m/z 239.1 (M+H).

Step 2

To a mixture of 2-(5-fluorothiophen-2-yl)-6-nitroaniline (CII) (500 mg,2.09 mmol) in EtOAc (20 mL) was added Zn power (410 mg, 6.27 mmol) andcooled to 0˜5° C. HOAc (3 mL) was then added dropwise and the mixturewas stirred at 15˜20° C. for 1 h. LC/MS showed the starting material wasconsumed completely. The mixture was filtered through Celite®, washedwith EtOAc (5×50 mL), the organic phase was washed with NaHCO₃ (50mL×2), brine (50 mL), water, then concentrated to dryness to afford3-(5-fluorothiophen-2-yl)benzene-1,2-diamine (CIII) (400 mg, 1.92 mmol,91.9% yield). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 4.42 (brs, 2H), 4.70 (brs,2H), 6.45 (s, 1H), 6.46 (s, 1H), 6.56 (t, J=4.4 Hz, 1H), 6.71 (dd, J=2.8Hz, J=4 Hz, 1H), 6.83 (t, J=4 Hz, 1H); ESIMS found for C₁₀H₉FN₂S m/z209.0 (M+H).

Preparation of intermediate 3-(5-methylthiophen-2-yl)benzene-1,2-diamine(CVI) is depicted below in Scheme 21.

Step 1

A solution of 3-bromo-2-nitroaniline (LXVI) (1.80 g, 8.29 mmol, 1 eq),4,4,5,5-tetramethyl-2-(5-methylthiophen-2-yl)-1,3,2-dioxaborolane (CIV)(2.23 g, 9.95 mmol, 1.2 eq), Na₂CO₃ (3.08 g, 29.01 mmol, 3.5 eq) andPd(dppf)Cl₂ (307.47 mg, 414.50 μmol, 0.05 eq) in dioxane (30 mL) andwater (6 mL) was de-gassed and then heated to 80° C. overnight under N₂.TLC (PE:EtOAc=1:1) showed the starting material was consumed completely.The reaction mixture was poured into H₂O (300 mL). The mixture wasextracted with EtOAc (3×250 mL). The organic phase was washed withsaturated brine (300 mL), dried over anhydrous Na₂SO₄, concentrated invacuum to give a residue. The crude product was purified by silica gelchromatography (PE:EtOAc=10:1) to give3-(5-methylthiophen-2-yl)-2-nitroaniline (CV) (1.20 g, 5.12 mmol, 61.79%yield) as a brown solid. ESIMS found for C₁₁H₁₀N₂O₂S m/z 345.1 (M+H).

Step 2

To a solution of 3-(5-methylthiophen-2-yl)-2-nitroaniline (CV) (1.20 g,5.12 mmol, 1 eq) in MeOH (30 mL) and H₂O (10 mL) was added Fe (1.14 g,20.48 mmol, 4.0 eq) and NH₄Cl (2.20 g, 40.96 mmol, 8.0 eq) in oneportion at room temperature. The mixture was stirred at room temperaturefor 10 min. Then heated to 80° C. and stirred for 16 hours. TLC showedthe reaction was completed. The mixture was cooled to room temperatureand concentrated under reduced pressure at 60° C. After filtration, theaqueous phase was extracted with EtOAc (400 mL×3). The combined organicphase was washed with saturated brine (200 mL×2), dried with anhydrousNa₂SO₄, filtered and concentrated in vacuum to produce3-(5-methylthiophen-2-yl)benzene-1,2-diamine (CVI) (1.00 g, 4.90 mmol,95.61% yield) as a brown solid. ¹H NMR (CD₃OD, 400 MHz) δ ppm 2.51 (s,3H), 6.62 (t, J=4 Hz, 1H), 6.66-6.75 (m, 2H), 6.79 (s, 1H), 6.93 (d,J=3.2 Hz, 1H); ESIMS found for C₁₁H₁₂N₂S m/z 205.0 (M+H).

Preparation of intermediateN-((2′,3′-diamino-5-fluoro-[1,1′-biphenyl]-3-yl)methyl)methanesulfonamide(CXII) is depicted below in Scheme 22.

Step 1

A solution of 3-bromo-5-fluorobenzonitrile (CVII) (44.0 g, 220.0 mmol,1.0 eq) was dissolved in THF (30 mL). BH₃-Me₂S (33.43 g, 440.0 mmol, 2.0eq) was added to the solution at 20° C. Then it was stirred at 80° C.for 2 h, HCl (6 N, 100 mL) was added to the mixture slowly at 20° C. Themixture was stirred at 80° C. for 1 h, then it was washed with EtOAc(300 ml). The water phase was basified with 50% aqueous NaOH and it wasextracted with EtOAc (300 mL×3). The combined organic layers were driedover anhydrous Na₂SO₄ and concentrated in vacuo to produce(3-bromo-5-fluoro-phenyl)methanamine (CVIII) (24.0 g, 117.62 mmol, 53.5%yield). ¹H NMR (CDCl₃, 300 MHz) 3.86 (s, 2H), 7.01 (d, J=8 Hz, 1H), 7.12(d, J=8 Hz, 1H), 7.28 (s, 1H); ESIMS found C₇H₇BrFN m/z 203.9 (Br⁷⁹M+H).

Step 2

A solution of (3-bromo-5-fluoro-phenyl)methanamine (CVIII) (23.0 g,112.7 mmol, 1.0 eq) was dissolved in DCM (15 mL), TEA (34.22 g, 338.2mmol, 3.0 eq) was added to the mixture. Then MsCl (13.44 g, 117.3 mmol,1.04 eq) was added slowly to the solution at 0° C. It was stirred at0-30° C. for 2 h. The reaction was washed with water and extracted withEtOAc. The combined organic layers were dried over anhydrous Na₂SO₄ andconcentrated to give N-(3-bromo-5-fluorobenzyl) methanesulfonamide (CIX)(34.0 g, 102.44 mmol, 90.9% yield, 85% purity) as an oil. ¹H NMR (CDCl₃,300 MHz) 2.88 (s, 3H), 4.24 (d, J=4.5 Hz, 2H), 6.99 (d, J=9 Hz, 1H),7.13 (dt, J=8.1 Hz, J=2 Hz, 1H), 7.25 (s, 1H); ESIMS found C₈H₉BrFNO₂Sm/z 282.0 (Br⁷⁹M+H).

Step 3

A solution of N-(3-bromo-5-fluorobenzyl)methanesulfonamide (CIX) (34.0g, 102.4 mmol, 1.0 eq) and4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane(52.02 g, 204.9 mmol, 2.0 eq), KOAc (20.11 g, 204.9 mmol, 2.0 eq) wasdissolved in dioxane (20 mL). Then Pd(dppf)Cl₂ (7.60 g, 10.2 mmol, 0.1eq) was added to the mixture. It was stirred at 90° C. for 2 h. Then thesolvent was removed to get the residue which was purified by silica gelcolumn (PE:EtOAc=10:1→100% EtOAc) to getN-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)methanesulfonamide(CX) (30.0 g, crude). ¹H NMR (CDCl₃, 400 MHz) 1.37 (s, 12H), 2.92 (s,3H), 4.34 (d, J=6.3 Hz, 2H), 7.19 (dt, J=9.3 Hz, J=2.1 Hz, 1H), 7.44(dd, J=8.7 Hz, J=2.4 Hz, 1H), 7.54 (s, 1H); ESIMS found C₁₄H₂₁BFNO₄S m/z330.1 (M+H).

Step 4

A solution of 2-bromo-6-nitroaniline (C) (1.80 g, 8.29 mmol, 1 eq),N-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)methanesulfonamide (CX) (3.27 g, 9.95 mmol, 1.2 eq), Na₂CO₃ (3.08 g,29.01 mmol, 3.5 eq) and Pd(dppf)Cl₂ (307.47 mg, 414.50 μmol, 0.05 eq) indioxane (30 mL) and water (6 mL) was de-gassed and then heated to 80° C.overnight under N₂. TLC (PE:EtOAc=1:1) showed the starting material wasconsumed completely. The reaction mixture was poured into H₂O (300 mL).The mixture was extracted with EtOAc (3×250 mL). The organic phase waswashed with saturated brine (300 mL), dried over anhydrous Na₂SO₄,concentrated in vacuum to give a residue. The crude product was purifiedby silica gel chromatography (PE:EtOAc=10:1) to giveN-((2′-amino-5-fluoro-3′-nitro-[1,1′-biphenyl]-3-yl)methyl)methanesulfonamide(CXI) (1.60 g, 4.72 mmol, 56.9% yield) as a brown solid. ESIMS found forC₁₄H₁₄FN₃O₄S m/z 340.1 (M+H).

Step 5

To a solution ofN-((2′-amino-5-fluoro-3′-nitro-[1,1′-biphenyl]-3-yl)methyl)methanesulfonamide(CXI) (1.60 g, 4.72 mmol, 1 eq) in MeOH (30 mL) was added Fe (1.05 g,18.88 mmol, 4.0 eq) and NH₄Cl (2.02 g, 37.76 mmol, 8.0 eq) in oneportion at room temperature. The mixture was stirred at room temperaturefor 10 min. Then heated to 80° C. and stirred for 16 hours. TLC showedthe reaction was completed. The mixture was cooled to room temperatureand concentrated under reduced pressure at 60° C. After filtration, theaqueous phase was extracted with EtOAc (400 mL×3). The combined organicphase was washed with saturated brine (100 mL×2), dried with anhydrousNa₂SO₄, filtered and concentrated in vacuum to produceN-((2′,3′-diamino-5-fluoro-[1,1′-biphenyl]-3-yl)methyl)methanesulfonamide(CXII) ((1.20 g, 3.88 mmol, 82.2% yield) as a brown solid. ¹H NMR(DMSO-d₆, 400 MHz) δ ppm 2.92 (s, 3H), 4.23 (d, J=6 Hz, 2H), 4.97 (brs,4H), 6.44 (d, J=7.2 Hz, 1H), 6.54 (t, J=7.6 Hz, 1H), 6.66 (d, J=7.6 Hz,1H), 7.11 (dd, J=9.8 Hz, J=18.4 Hz, 2H), 7.22 (s, 1H), 7.68 (d, J=4.8Hz, 1H); ESIMS found for C₁₄H₁₆FN₃O₂S m/z 310.1 (M+H).

Preparation of intermediateN^(3′)-(2-(dimethylamino)ethyl)-5′-fluoro-[1,1′-biphenyl]-2,3,3′-triamine(CXVII) is depicted below in Scheme 23.

Step 1

A solution of 3-bromo-5-fluorobenzaldehyde (CXIII) (20.0 g, 98.2 mmol,1.0 eq) in MeOH (1.8 L) was added N¹,N¹-dimethylethane-1,2-diamine (21.5mL, 196.4 mmol, 2.0 eq). The pH was adjusted to 6 using HOAc and stirredfor 1 h. NaCNBH₃ (8.6 g, 137.5 mmol, 1.4 eq) was added and stirred atroom temperature overnight. The MeOH was removed under vacuum and theresidue was partitioned between CHCl₃ and saturated aqueous NaHCO₃. Theorganic layer was dried over MgSO₄ and evaporated under vacuum. Thecrude product was purified on a silica gel column (100% CHCl₃→3:97MeOH[7N NH₃]:CHCl₃) to produceN¹-(3-bromo-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine (CXIV) as ayellow oil (13.0 g, 49.9 mmol, 51% yield). ¹H NMR (DMSO-d₆, 500 MHz) δppm 1.28 (s, 6H), 2.39 (t, J=4 Hz, 2H), 3.07 (q, J=6 Hz, 2H), 6.10 (t,J=5 Hz, 1H), 6.38 (td, J=12 Hz, J=2 Hz, 1H), 6.51 (td, J=8.6 Hz, J=2 Hz,1H), 6.61 (t, J=2 Hz, 1H); ESIMS found C₁₀H₁₄BrFN₂ m/z 261.0 (M+H).

Step 2

A solution ofN¹-(3-bromo-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine (CXIV)(13.0 g, 49.9 mmol, 1.0 eq), bis(pinacolato)diboron (12.6 g, 59.9 mmol,1.2 eq), KOAc (12.1 g, 124.3 mmol, 2.5 eq) and dioxane (600 mL) waspurged with argon. Pd(dppf)Cl₂ (2.0 g, 2.47 mmol, 0.05 eq) was added tothe reaction and purged again with argon. The solution was heated at 90°C. for 2 h. Once TLC showed the disappearance of (CXIV), the solutionwas cooled to room temperature and then concentrated under reducedpressure to produce crudeN¹-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(CXV) (7.4 g, 24.0 mmol, 48.2% yield).

Step 3

To a solution ofN¹-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(CXV) (4.00 g, 12.98 mmol, 1.0 eq) in dioxane (80 mL) and water (0.5 mL)was added K₂CO₃ (3.60 g, 26.0 mmol, 2.0 eq), 3-bromo-2-nitroaniline(LXVI) (2.82 g, 12.98 mmol, 1.0 eq) and Pd(dppf)Cl₂ (481.42 mg, 649.0μmol, 0.05 eq). The solution was purged with argon and heated at 80° C.for 4 h. The solution was cooled to room temperature and thenconcentrated under reduced pressure to giveN^(3′)-(2-(dimethylamino)ethyl)-5′-fluoro-2-nitro[1,1′-biphenyl]-3,3′-diamine(CXVI) as a solid (2.5 g, 7.86 mmol, 60.5% yield). ESIMS found forC₁₆H₁₉PN₄O₂ m/z 319.1 (M+H).

Step 4

To a solution ofN^(3′)-(2-(dimethylamino)ethyl)-5′-fluoro-2-nitro-[1,1′-biphenyl]-3,3′-diamine(CXVI) (2.50 g, 7.86 mmol, 1.0 eq) in MeOH (80 mL) was added Pd/C underN₂. The suspension was degassed under vacuum and purged with H₂ severaltimes. The mixture was stirred under H₂ (25 psi) at room temperature for24 h. LC/MS showed the starting material was consumed completely. Thereaction mixture was filtered and the filter was concentrated. The crudeproduct was purified by silica gel chromatography (MeOH:DCM=10:1) togiveN^(3′)-(2-(dimethylamino)ethyl)-5′-fluoro-[1,1′-biphenyl]-2,3,3′-triamine(CXVII) (2.0 g, 6.94 mmol, 88.2% yield) as yellow solid. ¹H NMR (CD₃OD,400 MHz) δ ppm 2.32 (s, 6H), 2.60 (t, J=6.8 Hz, 2H), 3.26 (t, J=6.8 Hz,2H), 6.31-6.38 (m, 2H), 6.45 (t, J=1.6 Hz, 1H), 6.59 (dd, J=1.6 Hz,J=7.6 Hz, 1H), 6.66 (t, J=7.6 Hz, 1H), 7.73 (dd, J=1.6 Hz, J=7.6 Hz,1H); ESIMS found C₁₆H₂₁FN₄ m/z 289.1 (M+H).

Preparation ofN,N-dimethyl-1-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(169) is depicted below in Scheme 24.

Step 1

A solution of 1-(5-bromopyridin-3-yl)-N,N-dimethylmethanamine (XXXIX)(10.00 g, 46.49 mmol, 1.0 eq), Pd(dppf)Cl₂ (1.70 g, 2.32 mmol, 0.05 Eq),KOAc (9.1 g, 93.0 mmol, 2.0 eq) and Pin₂B₂ (11.75 g, 46.49 mmol, 1.0 eq)in dioxane (230 mL) was de-gassed and then heated to 110° C. under N₂for 12 hr. TLC (PE:EtOAc=2:1) showed the starting material was consumedcompletely. The reaction mixture was filtered and concentrated to affordthe crude (5-((dimethylamino)methyl)pyridin-3-yl)boronic acid (CXVIII).The crude product was used in the next step without purification.

Step 2

To a solution of tert-butyl5-bromo-3-(diethoxymethyl)-1H-pyrazolo[3,4-c]pyridine-1-carboxylate(XVI) (3.0 g, 7.49 mmol, 1.0 eq) and(5-((dimethylamino)methyl)pyridin-3-yl)boronic acid (CXVIII) (2.02 g,11.24 mmol, 1.5 eq) in dioxane (30 mL) and H₂O (5 mL) was addedPd(dppf)Cl₂ (111.1 mg, 149.9 μmol, 0.02 eq), K₂CO₃ (2.07 g, 15.0 mmol,2.0 eq) at room temperature. The mixture was stirred at 90° C. for 3 hr.TLC (PE:EtOAc=0:1) showed that the starting material was consumedcompletely. The mixture was added water (50 mL) and extracted with EtOAc(80 mL×2). The organic layers were washed with brine (60 mL),concentrated. The residue was purified by chromatography on silica gel(PE:EtOAc=1:1→1:5) to afford tert-butyl3-(diethoxymethyl)-5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine-1-carboxylate(CXIX) (0.84 g, 1.84 mmol, 24.6% yield) as a brown oil. ¹H NMR (CDCl₃,400 MHz) δ ppm 1.31 (t, J=7.2 Hz, 6H), 1.79 (s, 9H), 3.57 (s, 2H),3.64-3.75 (m, 2H), 3.80-3.93 (m, 2H), 5.86 (s, 1H), 8.35 (s, 1H), 8.38(d, J=1.6 Hz, 1H), 8.60 (d, J=1.6 Hz, 1H), 9.19 (d, J=2.4 Hz, 1H), 9.55(s, 1H); ESIMS found for C₂₄H₃₃N₅O₄ m/z 456.1 (M+H).

Step 3

A mixture of tert-butyl 3-(diethoxymethyl)-5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine-1-carboxylate (CXIX)(100.0 mg, 0.22 mmol, 1 eq), 3-(piperidin-1-yl)benzene-1,2-diamine(LVII) (42 mg, 0.22 mmol, 1.0 eq) and Na₂S₂O₅ (51 mg, 0.26 mmol, 1.2 eq)in DMF (2 mL) was stirred at 120° C. for 24 h. LC/MS showed CXIX wasconsumed. Water (5 mL) was added in dropwise and the mixture wasfiltered. The filtrate was washed by MeOH (0.5 mL) and purified bypre-HPLC (HCl) to giveN,N-dimethyl-1-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(169) (16.1 mg, 0.04 mmol, 16.2%) as a white solid. ¹H NMR (DMSO-d₆, 400MHz) δ ppm 1.84 (brs, 2H), 2.15 (brs, 4H), 2.80 (d, J=4.02 Hz, 6H), 4.03(brs, 4H), 4.50 (d, J=4.14 Hz, 2H), 7.41 (t, J=7.92 Hz, 1H), 7.65-7.75(m, 2H), 8.88 (d, J=1.63 Hz, 1H), 9.07 (s, 1H), 9.16 (s, 1H), 9.37 (d,J=1.13 Hz, 1H), 9.51 (d, J=1.63 Hz, 1H), 10.97 (brs, 1H), 13.91 (brs,1H), 14.72 (brs, 1H); ESIMS found for C₂₆H₂₈N₈ m/z 453.2 (M+1).

The following compound was prepared in accordance with the proceduredescribed in the above Example 1.

N-(5-(3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide1

White solid (18.0 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.15(t, J=7.59 Hz, 3H), 2.48 (q, J=7.68 Hz, 4H), 7.25 (td, J=8.13, 2.32 Hz,1H), 7.40 (t, J=7.68 Hz, 1H), 7.60-7.70 (m, 3H), 8.15-8.22 (m, 1H),8.26-8.35 (m, 1H), 9.05 (s, 2H), 9.12 (d, J=3.26 Hz, 2H), 9.36 (s, 1H),10.80 (brs, 1H), 14.61 (brs, 1H); ESIMS found for C₂₇H₂₀FN₇O m/z 478.1(M+1).

5-(3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N,N-dimethylpyridin-3-amine7

White solid (34.3 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 3.07(s, 6H), 7.27 (td, J=8.12 Hz, J=1.48 Hz, 1H), 7.38 (t, J=7.76 Hz, 1H),7.54-7.65 (m, 3H), 7.84 (brs, 1H), 8.09-8.17 (m, 1H), 8.20 (d, J=2.38Hz, 1H), 8.33-8.42 (m, 1H), 8.64 (s, 1H), 8.95 (s, 1H), 9.32 (s, 1H),13.45 (brs, 1H), 14.39 (s, 1H); ESIMS found for C₂₆H₂₀FN₇ m/z 450.1(M+1).

1-(5-(3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine13

White solid (15.5 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.59(brs, 6H), 4.03 (brs, 2H), 7.26-7.34 (m, 1H), 7.39 (t, J=7.47 Hz, 1H),7.57-7.66 (m, 3H), 8.15 (d, J=7.40 Hz, 1H), 8.45-8.52 (m, 1H), 8.52-8.59(m, 1H), 8.65 (brs, 1H), 9.04 (brs, 1H), 9.33 (brs, 2H), 13.47 (brs,1H), 14.41 (brs, 1H); ESIMS found for C₂₇H₂₂FN₇ m/z 464.1 (M+1).

N-(5-(3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide19

White solid (56.8 mg, 0.12 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm0.85-0.93 (m, 4H), 1.82-1.91 (m, 1H), 7.25 (td, J=8.34, 2.26 Hz, 1H),7.39 (t, J=7.64 Hz, 1H), 7.57-7.66 (m, 3H), 8.13-8.23 (m, 1H), 8.33-8.47(m, 1H), 8.81 (d, J=1.88 Hz, 1H), 8.90 (s, 1H), 8.99 (s, 2H), 9.32 (s,1H), 10.63 (s, 1H), 13.47 (brs, 1H) 14.40 (s, 1H); ESIMS found forC₂₈H₂₀FN₇O m/z 490.1 (M+1).

5-(5-((3,3-Difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine25

White solid (33.3 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm2.55-2.65 (m, 2H), 3.78-3.91 (m, 2H), 4.53-4.65 (m, 2H), 7.29 (td,J=8.50, 2.82 Hz, 1H), 7.41 (t, J=7.92 Hz, 1H), 7.59-7.68 (m, 3H), 8.11(d, J=7.53 Hz, 1H), 8.35-8.44 (m, 1H), 8.94 (brs, 2H), 9.11 (s, 1H),9.37 (d, J=1.13 Hz, 1H), 9.46 (s, 1H), 14.62 (brs, 1H); ESIMS found forC₂₉H₂₂F₃N₇ m/z 526.1 (M+1).

N-(5-(3-(4-(4-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide28

White solid (13.7 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.99(d, J=6.53 Hz, 6H), 2.18 (non, J=6.64 Hz, 1H), 2.35 (d, J=7.15 Hz, 2H),7.39 (t, J=7.76 Hz, 1H), 7.45 (t, J=8.91 Hz, 2H), 7.52 (d, J=6.65 Hz,1H), 7.58 (d, J=8.28 Hz, 1H), 8.39 (brs, 2H), 8.99 (s, 1H), 9.01-9.07(m, 1H), 9.15 (brs, 2H), 9.36 (s, 1H), 10.78 (brs, 1H), 14.56 (brs, 1H);ESIMS found for C₂₉H₂₄FN₇O m/z 506.1 (M+1).

N-(5-(3-(4-(4-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide34

White solid (35.3 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.31(s, 9H), 7.34-7.45 (m, 3H), 7.49-7.59 (m, 2H), 8.40-8.49 (m, 2H),8.90-8.95 (m, 3H), 9.03 (d, J=1.63 Hz, 1H), 9.31 (d, J=1.25 Hz, 1H),9.67 (s, 1H), 13.40 (brs, 1H), 14.37 (s, 1H); ESIMS found for C₂₉H₂₄FN₇Om/z 506.2 (M+1).

3-(4-(4-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine40

White solid (22.0 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.86-1.97 (m, 2H), 2.03-2.13 (m, 2H), 3.14-3.24 (m, 2H), 3.41-3.52 (m,2H), 4.61 (d, J=5.77 Hz, 2H), 7.37-7.48 (m, 3H), 7.51 (d, J=6.65 Hz,1H), 7.62 (d, J=7.91 Hz, 1H), 8.31-8.40 (m, 2H), 8.97 (s, 2H), 9.10 (d,J=1.13 Hz, 1H), 9.36 (d, J=1.25 Hz, 1H), 9.48 (d, J=1.63 Hz, 1H), 10.98(brs, 1H), 14.62 (brs, 1H); ESIMS found for C₂₉H₂₄FN₇ m/z 490.1 (M+1).

N-(5-(3-(4-(4-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide46

White solid (45.7 mg, 0.09 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.80-1.92 (m, 1H), 1.94-2.04 (m, 1H), 2.13-2.25 (m, 2H), 2.27-2.38 (m,2H), 3.29-3.36 (m, 1H), 7.37 (t, J=7.68, 1H), 7.44 (t, J=8.91 Hz, 2H),7.52 (d, J=7.15 Hz, 1H), 7.57 (d, J=7.91 Hz, 1H), 8.37-8.48 (m, 2H),8.80 (s, 1H), 8.94 (s, 1H), 8.99 (s, 1H), 9.03 (d, J=1.88 Hz, 1H), 9.32(d, J=1.13 Hz, 1H), 10.23 (s, 1H), 13.40 (brs, 1H), 14.38 (s, 1H); ESIMSfound for C₂₉H₂₂FN₇O m/z 504.1 (M+1).

3-(4-(4-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine52

White solid (76.9 mg, 0.19 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 7.36(t, J=8.85 Hz, 2H), 7.43-7.52 (m, 2H), 7.67 (dd, J=7.64 Hz, J=1.00 Hz,1H), 8.16 (dd, J=8.66, 5.65 Hz, 2H), 9.00 (s, 1H), 9.24 (s, 1H), 9.33(d, J=0.88 Hz, 1H), 9.47 (s, 2H); ESIMS found for C₂₃H₁₄FN₇ m/z 408.0(M+1).

5-(3-(4-(2-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine55

White solid (31.2 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ 7.39-7.50(m, 4H), 7.51-7.59 (m, 1H), 7.76-7.84 (m, 1H), 7.86-7.97 (m, 1H), 8.08(d, J=2.38 Hz, 1H), 8.40 (s, 1H), 8.67 (brs, 1H), 9.04 (br. s., 1H),9.35 (d, J=1.13 Hz, 1H), 14.82 (brs, 1H); ESIMS found for C₂₄H₁₆FN₇ m/z422.0 (M+1).

N-(5-(3-(4-(2-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide61

White solid (43.3 mg, 0.09 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.18(d, J=6.78 Hz, 6H), 2.66-2.74 (m, 1H), 7.34-7.53 (m, 5H), 7.57-7.64 (m,1H), 8.10-8.18 (m, 1H), 8.78 (d, J=3.89 Hz, 1H), 8.84-8.93 (m, 3H), 9.29(s, 1H), 10.23 (s, 1H), 13.37 (brs 1H), 14.33 (s, 1H); ESIMS found forC₂₈H₂₂FN₇O m/z 492.1 (M+1).

N-(5-(3-(4-(2-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide68

White solid (7.1 mg, 0.01 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.08(s, 9H), 2.31 (s, 2H), 7.35-7.45 (m, 4H), 7.47-7.55 (m, 1H), 7.62-7.73(m, 1H), 7.94-8.09 (m, 1H), 8.87-8.93 (m, 2H), 8.93-9.02 (m, 2H), 9.32(d, J=1.13 Hz, 1H), 10.41 (brs, 1H), 14.44 (brs, 1H); ESIMS found forC₃₀H₂₆FN₇O m/z 520.2 (M+1).

N-(5-(3-(4-(2-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide73

White solid (10.2 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.56-1.66 (m, 2H), 1.66-1.85 (m, 4H), 1.88-1.98 (m, 2H), 2.83-2.93 (m,1H), 7.32-7.53 (m, 5H), 7.59 (d, J=7.15 Hz, 1H), 8.10-8.18 (m, 1H), 8.76(s, 1H), 8.83-8.92 (m, 3H), 9.29 (s, 1H), 10.28 (brs, 1H), 13.39 (brs,1H), 14.35 (brs 1H); ESIMS found for C₃₀H₂₄FN₇O m/z 518.2 (M+1).

5-(Pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine82

White solid (52.5 mg, 0.13 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 7.52(t, J=7.72 Hz, 1H), 7.78 (d, J=8.03 Hz, 1H), 7.86 (d, J=7.40 Hz, 1H),8.20 (dd, J=8.09, 6.09 Hz, 1H), 8.32 (dd, J=7.91, 5.77 Hz, 1H), 8.98(dd, J=12.92, 5.40 Hz, 2H), 9.15 (s, 1H), 9.24-9.31 (m, 1H), 9.41 (s,1H), 9.45-9.51 (m, 1H), 9.66 (s, 1H), 10.07 (d, J=0.75 Hz, 1H), 14.76(brs, 1H); ESIMS found for C₂₃H₁₅N₇ m/z 390.0 (M+1).

N-(5-(3-(4-(Pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide87

White solid (42.4 mg, 0.09 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.19(d, J=6.90 Hz, 6H), 2.65-2.75 (m, 1H), 7.45 (t, J=7.72 Hz, 1H),7.65-7.72 (m, 2H), 7.88-7.94 (m, 1H), 8.76 (dd, J=5.08, 1.44 Hz, 1H),8.85 (d, J=2.26 Hz, 1H), 8.93 (d, J=1.13 Hz, 1H), 8.95 (t, J=2.07 Hz,1H), 9.04 (d, J=2.01 Hz, 1H), 9.08-9.18 (m, 1H), 9.33 (d, J=1.13 Hz,1H), 9.60 (brs, 1H), 10.30 (s, 1H), 13.56 (brs, 1H) 14.45 (s, 1H); ESIMSfound for C₂₇H₂₂N₈O m/z 475.1 (M+1).

N-Isopropyl-5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine90

White solid (6.3 mg, 0.01 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.23(d, J=6.27 Hz, 6H), 3.79 (spt, J=6.04 Hz, 2H), 7.42 (t, J=7.88 Hz, 1H),7.58-7.66 (m, 3H), 7.87 (brs, 1H), 8.06 (d, J=2.51 Hz, 1H), 8.54 (s,1H), 8.65 (dd, J=4.77, 1.51 Hz, 1H), 8.72-8.78 (m, 1H), 8.94 (s, 1H),9.31 (d, J=1.13 Hz, 1H), 9.56 (brs, 1H), 13.49 (brs, 1H), 14.42 (s, 1H);ESIMS found for C₂₆H₂₂N₈ m/z 447.1 (M+1).

5-(5-(Piperidin-1-ylmethyl)pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine93

White solid (49.7 mg, 0.10 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.34-1.48 (m, 1H), 1.66-1.76 (m, 1H), 1.81 (brs, 4H), 2.95-3.08 (m, 2H),3.46 (d, J=9.54 Hz, 2H), 4.69 (brs, 2H), 7.51 (t, J=7.84 Hz, 1H), 7.78(d, J=8.03 Hz, 1H), 7.86 (d, J=7.40 Hz, 1H), 8.32 (dd, J=8.28, 5.65 Hz,1H), 9.02 (d, J=5.40 Hz, 1H), 9.07 (s, 1H), 9.12 (s, 1H), 9.35 (s, 1H),9.39 (d, J=1.25 Hz, 1H), 9.44 (d, J=8.41 Hz, 1H), 9.61 (d, J=1.63 Hz,1H), 10.16 (brs, 1H), 11.17 (brs, 1H), 14.84 (brs, 1H); ESIMS found forC₂₉H₂₆N₈ m/z 487.1 (M+1).

N-Benzyl-1-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine101

White solid (5.3 mg, 0.01 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 4.34(brs, 2H), 4.49-4.54 (m, 2H), 7.42-7.53 (m, 4H), 7.59 (dd, J=7.65, 1.63Hz, 2H), 7.72-7.84 (m, 3H), 8.12-8.20 (m, 2H), 8.83 (s, 1H), 8.90-8.96(m, 2H), 9.04 (d, J=0.75 Hz, 1H), 9.37 (d, J=1.25 Hz, 1H), 9.48 (d,J=2.51 Hz, 1H), 14.62 (brs, 1H); ESIMS found for C₃₁H₂₄N₈ m/z 509.2(M+1).

5-(4-Methylpyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine109

White solid (23.8 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.76(s, 3H), 7.53 (t, J=7.80 Hz, 1H), 7.86 (d, J=7.65 Hz, 1H), 8.01 (d,J=7.53 Hz, 1H), 8.12 (d, J=5.90 Hz, 1H), 8.83 (s, 1H), 8.91 (d, J=5.90Hz, 1H), 9.03 (d, J=6.40 Hz, 2H), 9.16 (d, J=5.77 Hz, 2H), 9.26 (s, 1H),9.41 (s, 1H), 13.94 (brs, 1H), 14.89 (brs, 1H); ESIMS found for C₂₄H₁₇N₇m/z 404.1 (M+1).

2-Phenyl-N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide114

White solid (16.5 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 3.77(s, 2H), 7.26 (t, J=7.52 Hz, 1H), 7.35 (t, J=7.53 Hz, 2H), 7.39-7.46 (m,3H), 7.66 (d, J=7.78 Hz, 1H), 7.72 (d, J=7.40 Hz, 1H), 8.42 (s, 1H),8.44 (s, 1H), 8.77 (brs, 1H), 8.79 (s, 2H), 8.93 (s, 1H), 9.01 (s, 1H),9.03 (d, J=1.63 Hz, 1H), 9.31 (s, 1H), 10.61 (s, 1H), 13.54 (s, 1H);ESIMS found for C₃₁H₂₂N₈O m/z 523.2 (M+1).

N-(5-(3-(4-(Pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide121

White solid (24.0 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.97(t, J=7.40 Hz, 3H), 1.69 (sxt, J=7.38 Hz, 2H), 2.52-2.55 (m, 2H), 7.51(t, J=7.84 Hz, 1H), 7.83 (d, J=8.03 Hz, 1H), 8.00 (d, J=7.65 Hz, 1H),9.04 (s, 1H), 9.12-9.17 (m, 2H), 9.18-9.23 (m, 3H), 9.31 (s, 1H), 9.36(d, J=1.00 Hz, 1H), 9.41 (s, 1H), 11.38 (s, 1H), 13.86 (brs, 1H), 14.83(s, 1H); ESIMS found for C₂₇H₂₂N₈O m/z 475.1 (M+1).

N-(5-(3-(4-(Pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide126

White solid (54.7 mg, 0.11 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.19-1.39 (m, 3H), 1.44-1.57 (m, 2H), 1.64-1.72 (m, 1H), 1.75-1.84 (m,2H), 1.91 (d, J=12.55 Hz, 2H), 2.39-2.47 (m, 1H), 7.43 (t, J=7.84 Hz,1H), 7.66 (d, J=7.91 Hz, 1H), 7.72 (d, J=7.53 Hz, 1H), 8.40-8.45 (m,2H), 8.73 (d, J=2.26 Hz, 1H), 8.78 (d, J=6.15 Hz, 2H), 8.96-9.03 (m,3H), 9.32 (d, J=1.00 Hz, 1H), 10.25 (s, 1H), 13.53 (s, 1H), 14.41 (s,1H); ESIMS found for C₃₀H₂₆N₈O m/z 515.2 (M+1).

N-((5-(3-(4-(Pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine136

White solid (72.6 mg, 0.16 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.29(t, J=6.96 Hz, 3H), 3.03-3.13 (m, 3H), 4.42 (t, J=4.64 Hz, 2H), 7.56 (t,J=7.65 Hz, 1H), 7.87-7.96 (m, 2H), 8.16 (d, J=7.03 Hz, 1H), 8.55-8.63(m, 1H), 8.95 (brs, 1H), 9.03-9.12 (m, 2H), 9.14 (brs, 1H), 9.22 (s,1H), 9.39 (s, 1H), 9.50-9.63 (m, 2H), 14.81 (brs, 1H); ESIMS found forC₂₆H₂₂N₈ m/z 447.1 (M+1).

N-(5-(3-(4-(Pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide141

White solid (28.6 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 7.52(t, J=7.78 Hz, 1H), 7.60-7.74 (m, 4H), 7.84 (d, J=8.16 Hz, 1H),8.09-8.13 (m, 2H), 8.16 (d, J=7.40 Hz, 1H), 8.45-8.53 (m, 1H), 9.03 (d,J=4.89 Hz, 1H), 9.05-9.12 (m, 1H), 9.14 (s, 1H), 9.23 (s, 1H), 9.32 (s,1H), 9.39 (d, J=1.13 Hz, 2H), 11.05 (s, 1H), 14.72 (brs, 1H); ESIMSfound for C₃₀H₂₀N₈O m/z 509.2 (M+1).

N-(5-(3-(4-(Pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide148

White solid (63.7 mg, 0.13 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.94(t, J=7.40 Hz, 3H), 1.39 (sxt, J=7.80 Hz, 2H), 1.66 (quin, J=7.52 Hz,2H), 2.43 (t, J=7.28 Hz, 2H), 7.40-7.49 (m, 2H), 7.69-7.79 (m, 1H),8.07-8.14 (m, 1H), 8.15-8.23 (m, 1H), 8.73-8.86 (m, 3H), 8.90-9.00 (m,2H), 9.05 (d, J=0.75 Hz, 1H), 9.34 (s, 1H), 10.34 (s, 1H), 14.43 (s,1H); ESIMS found for C₂₈H₂₄N₈O m/z 489.1 (M+1).

1-Cyclopentyl-N-((5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine154

White solid (40.3 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.21-1.34 (m, 2H), 1.47-1.65 (m, 4H), 1.76-1.87 (m, 2H), 2.21-2.30 (m,1H), 3.00 (q, J=7.80 Hz, 3H), 4.43 (t, J=5.00 Hz, 2H), 7.55 (t, J=7.84Hz, 1H), 7.89 (d, J=7.91 Hz, 2H), 8.16 (d, J=7.53 Hz, 1H), 8.54-8.61 (m,1H), 8.97 (d, J=1.51 Hz, 1H), 9.04-9.12 (m, 2H), 9.16 (brs, 1H), 9.22(s, 1H), 9.37-9.47 (m, 3H), 9.57 (d, J=1.63 Hz, 1H), 14.80 (brs, 1H);ESIMS found for C₃₀H₂₈N₈ m/z 501.2 (M+1).

N-(5-(3-(4-(Piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide157

White solid (8.2 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.14(t, J=7.47 Hz, 3H), 1.67-1.75 (m, 2H), 1.89-1.99 (m, 4H), 2.42 (q,J=7.40 Hz, 4H), 3.75-3.87 (m, 4H), 7.25 (d, J=2.76 Hz, 2H), 8.75 (d,J=2.13 Hz, 1H), 8.96 (s, 1H), 8.98 (brs, 1H), 9.01 (s, 1H), 9.33 (s,1H), 10.35 (s, 1H), 14.42 (brs, 1H); ESIMS found for C₂₆H₂₆N₈O m/z 467.2(M+1).

N-(5-(3-(4-(Piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide175

White solid (10.6 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm0.84-0.91 (m, 4H), 1.62-1.70 (m, 2H), 1.78-1.89 (m, 5H), 3.58-3.65 (m,4H), 6.55 (d, J=7.78 Hz, 1H), 7.02 (d, J=7.76 Hz, 1H), 7.09 (t, J=7.80Hz, 1H), 8.70 (d, J=2.26 Hz, 1H), 8.92 (s, 1H), 8.95 (s, 1H), 8.96 (d,J=1.88 Hz, 1H), 9.28 (s, 1H), 10.60 (s, 1H), 13.06 (s, 1H), 14.24 (brs,1H); ESIMS found for C₂₇H₂₆N₈O m/z 479.1 (M+1).

5-(5-((3,3-Difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine181

White solid (12.7 mg, 0.02 mmol). ¹H NMR (CD₃OD, 400 MHz) δ ppm 1.97(brs, 2H), 2.35 (brs, 4H), 2.72-2.85 (m, 2H), 3.91 (brs, 2H), 4.12 (brs,6H), 7.54 (t, J=8.04 Hz, 1H), 7.70 (d, J=7.65 Hz, 1H), 7.85 (d, J=8.03Hz, 1H), 9.16 (brs, 1H), 9.38 (s, 1H), 9.62 (brs, 1H), 9.79 (s, 1H),9.96 (brs, 1H); ESIMS found for C₂₈H₂₈F₂N₈ m/z 515.2 (M+1).

3-Methyl-N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide184

White solid (12.7 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ p 0.98 (d,J=6.65 Hz, 6H), 2.09-2.19 (m, 1H), 2.32 (d, J=6.90 Hz, 3H), 7.51 (t,J=7.80 Hz, 1H), 7.71 (d, J=7.65 Hz, 1H), 7.75 (d, J=7.78 Hz, 1H), 8.50(d, J=1.51 Hz, 1H), 8.95 (d, J=1.51 Hz, 1H), 8.99 (s, 1H), 9.03 (brs,1H), 9.16 (s, 1H), 9.36 (d, J=1.13 Hz, 1H), 10.08 (brs, 1H) 10.58 (brs,1H), 13.92 (brs, 1H), 14.65 (s, 1H); ESIMS found for C₂₇H₂₅N₉O m/z 492.2(M+1).

N-(5-(3-(4-(4-Methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide190

White solid (6.6 mg, 0.01 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.29(s, 9H), 2.29 (s, 3H), 7.36 (t, J=7.92 Hz, 1H), 7.50 (dd, J=7.92 Hz,J=1.76 Hz, 2H), 8.07 (s, 1H), 8.77 (s, 1H), 8.86 (s, 1H), 8.95 (s, 2H),8.99 (d, J=1.38 Hz, 1H), 9.33 (s, 1H), 9.62 (s, 1H), 13.62 (brs, 1H),14.44 (brs, 1H); ESIMS found for C₂₇H₂₅N₉O m/z 492.1 (M+1).

3-(4-(4-Methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine196

White solid (16.7 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.92(brs, 2H), 2.06 (brs, 2H), 2.52 (d, J=0.88 Hz, 3H), 3.21 (brs, 2H), 3.48(brs, 2H), 4.80 (d, J=2.51 Hz, 2H), 7.50 (t, J=7.97 Hz, 1H), 7.71 (d,J=7.40 Hz, 1H), 7.76 (d, J=8.16 Hz, 1H), 8.46 (s, 1H), 9.11 (s, 1H),9.17 (s, 1H), 9.38 (d, J=1.25 Hz, 1H), 9.41 (brs, 1H), 9.62 (d, J=1.63Hz, 1H), 10.24 (s, 1H), 11.70 (brs, 1H), 14.89 (brs, 1H); ESIMS foundfor C₂₇H₂₅N₉ m/z 476.2 (M+1).

N-(5-(3-(4-(4-Methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide202

White solid (42.2 mg, 0.09 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.79-1.90 (m, 1H), 1.94-2.03 (m, 1H), 2.11-2.22 (m, 2H), 2.23-2.35 (m,3H), 2.39 (s, 3H), 7.44 (t, J=7.88 Hz, 1H), 7.61 (dd, J=8.03, 4.14 Hz,2H), 8.30 (s, 1H), 8.84 (d, J=2.38 Hz, 1H), 8.89 (t, J=2.01 Hz, 1H),8.95 (s, 1H), 9.02 (d, J=1.88 Hz, 1H), 9.34 (d, J=1.25 Hz, 1H), 9.41 (d,J=3.64 Hz, 1H), 10.12 (s, 1H), 13.75 (s, 1H), 14.48 (s, 1H); ESIMS foundfor C₂₇H₂₃N₉O m/z 490.1 (M+1).

5-(3-(4-(4-Methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine211

White solid (44.3 mg, 0.10 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.95(d, J=4.64 Hz, 3H), 3.24-3.34 (m, 4H), 3.39-3.48 (m, 2H), 3.66-3.76 (m,2H), 4.42-4.55 (m, 2H), 6.72 (d, J=6.90 Hz, 1H), 7.17-7.26 (m, 2H), 8.09(d, J=2.26 Hz, 1H), 8.43 (t, J=1.88 Hz, 1H), 8.67 (s, 1H), 8.99 (s, 1H),9.33 (d, J=1.13 Hz, 1H), 10.90 (brs, 1H), 14.66 (brs, 1H); ESIMS foundfor C₂₃H₂₃N₉ m/z 426.1 (M+1).

N-(5-(3-(4-(4-Methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide217

White solid (21.8 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.19(d, J=6.78 Hz, 6H), 2.79 (spt, J=7.16 Hz, 1H), 2.94 (d, J=4.39 Hz, 3H),3.29 (t, J=12.28 Hz, 4H), 3.41-3.53 (m, 8H), 4.42-4.55 (m, 2H), 6.72 (d,J=5.65 Hz, 1H), 7.16-7.27 (m, 2H), 9.02 (s, 1H), 9.25 (brs, 2H), 9.28(brs, 1H), 9.36 (d, J=1.00 Hz, 1H), 10.73-10.85 (m, 1H), 11.20 (brs,1H), 14.67 (brs, 1H); ESIMS found for C₂₇H₂₉N₉O m/z 496.2 (M+1).

3-(4-(4-Methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine223

White solid (14.8 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.33-1.45 (m, 1H), 1.67-1.87 (m, 6H), 2.92 (d, J=4.40 Hz, 3H), 2.94-3.04(m, 2H), 3.26-3.36 (m, 2H), 3.38-3.53 (m, 5H), 3.62-3.71 (m, 2H), 4.52(d, J=5.02 Hz, 4H), 6.69-6.75 (m, 1H), 7.17-7.25 (m, 2H), 8.95 (s, 1H),8.97 (brs, 1H), 9.01 (s, 1H), 9.35 (d, J=1.13 Hz, 1H), 9.48 (s, 1H),10.81 (brs, 1H), 14.58 (brs, 1H); ESIMS found for C₂₉H₃₃N₉ m/z 508.2(M+1).

N-(5-(3-(4-(4-Methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide229

White solid (13.9 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.53-1.65 (m, 2H), 1.66-1.85 (m, 4H), 1.88-1.99 (m, 2H), 2.91-3.04 (m,4H), 3.23-3.33 (m, 4H), 3.41-3.52 (m, 2H), 4.40-4.53 (m, 2H), 6.73 (d,J=6.65 Hz, 1H), 7.17-7.28 (m, 2H), 9.04 (s, 1H), 9.26 (s, 2H), 9.30 (s,1H), 9.37 (s, 1H), 10.81 (brs, 1H) 11.30 (s, 1H), 14.71 (brs, 1H); ESIMSfound for C₂₉H₃₁N₉O m/z 522.3 (M+1).

3-(4-(4-Methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine234

White solid (63.9 mg, 0.16 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.90(d, J=4.52 Hz, 3H), 3.29 (t, J=12.32 Hz, 2H), 3.43 (q, J=10.04 Hz, 2H),3.61 (d, J=9.91 Hz, 2H), 4.40 (brs, 2H), 6.74-6.83 (m, 1H), 7.21-7.33(m, 2H), 9.02-9.09 (m, 1H), 9.28 (s, 1H), 9.38 (s, 1H), 9.55 (brs, 2H),10.75 (brs, 1H), 14.72 (brs, 1H); ESIMS found for C₂₂H₂₁N₉ m/z 412.1(M+1).

3-(1H-Benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine238

White solid (29.1 mg, 0.09 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 7.54(dd, J=6.09, 3.20 Hz, 2H), 7.86-7.92 (m, 2H), 8.15 (dd, J=8.16, 5.52 Hz,1H), 8.94 (d, J=5.27 Hz, 1H), 9.37 (d, J=8.28 Hz, 1H), 9.47 (d, J=1.00Hz, 1H), 9.65 (brs, 1H), 9.77 (d, J=1.63 Hz, 1H), 15.28 (brs, 1H); ESIMSfound for C₁₈H₁₂N₆ m/z 313.0 (M+1).

N-(5-(3-(1H-Benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide244

White solid (11.0 mg, 0.02 mmol). ¹H NMR (CD₃OD, 400 MHz) δ ppm 3.87 (s,2H), 7.27-7.33 (m, 1H), 7.37 (t, J=7.53 Hz, 2H), 7.41-7.46 (m, 2H), 7.68(dd, J=6.28 Hz, J=3.16 Hz, 2H), 7.95 (dd, J=6.24 Hz, J=3.12 Hz, 2H),9.25 (d, J=1.25 Hz, 1H), 9.31 (d, J=2.13 Hz, 1H), 9.39 (d, J=1.38 Hz,1H), 9.41-9.45 (m, 2H); ESIMS found for C₂₆H₁₉N₇O m/z 446.1 (M+1).

N-(5-(3-(1H-Benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide250

White solid (11.9 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.07(s, 9H), 2.31 (s, 2H), 7.33-7.39 (m, 2H), 7.71-7.77 (m, 2H), 8.96 (s,1H), 8.99 (s, 1H), 9.02 (d, J=1.88 Hz, 1H), 9.17 (d, J=0.88 Hz, 1H),9.37 (d, J=1.13 Hz, 1H), 10.50 (s, 1H), 14.66 (brs, 1H); ESIMS found forC₂₄H₂₃N₇O m/z 426.1 (M+1).

N-(5-(3-(1H-Benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide256

White solid (49.9 mg, 0.11 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.18-1.38 (m, 3H), 1.40-1.53 (m, 2H), 1.64-1.72 (m, 1H), 1.75-1.83 (m,2H), 1.84-1.93 (m, 2H), 2.36-2.46 (m, 1H), 7.27 (dd, J=5.90, 3.14 Hz,2H), 7.63-7.75 (m, 2H), 8.78 (s, 1H), 8.84 (s, 1H), 8.89 (d, J=1.63 Hz,1H), 9.01 (s, 1H), 9.31 (d, J=1.13 Hz, 1H), 10.25 (s, 1H), 14.38 (s,1H); ESIMS found for C₂₅H₂₃N₇O m/z 438.1 (M+1).

5-(4-Methylpyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine265

White solid (26.8 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.80(s, 3H), 7.33 (t, J=7.78 Hz, 1H), 7.52 (d, J=7.53 Hz, 1H), 7.64 (d,J=7.03 Hz, 1H), 7.68 (dd, J=5.08, 2.95 Hz, 1H), 8.09 (d, J=4.39 Hz, 1H),8.14 (d, J=6.02 Hz, 1H), 8.67 (d, J=1.88 Hz, 1H), 8.85 (d, J=1.13 Hz,1H), 8.88 (d, J=6.02 Hz, 1H), 9.20 (s, 1H), 9.40 (d, J=1.26 Hz, 1H),14.68 (brs, 1H); ESIMS found for C₂₃H₁₆N₆S m/z 409.0 (M+1).

N-(5-(3-(4-(Thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide268

White solid (36.7 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.31(s, 9H), 7.32 (t, J=7.76 Hz, 1H), 7.50 (d, J=7.91 Hz, 1H), 7.65 (d,J=7.65 Hz, 1H), 7.72 (dd, J=4.96, 3.07 Hz, 1H), 8.17 (d, J=4.77 Hz, 1H),8.75 (d, J=2.38 Hz, 1H), 8.91 (s, 2H), 9.00 (s, 1H), 9.04 (d, J=1.63 Hz,1H), 9.32 (d, J=1.13 Hz, 1H), 9.64 (s, 1H), 13.37 (s, 1H); ESIMS foundfor C₂₇H₂₃N₇OS m/z 494.1 (M+1).

N-(5-(3-(4-(Thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide269

White solid (46.2 mg, 0.10 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.21(d, J=6.78 Hz, 6H), 2.75 (spt, J=6.8 Hz, 1H), 7.34 (t, J=7.78 Hz, 1H),7.53 (d, J=7.91 Hz, 1H), 7.65 (d, J=7.40 Hz, 1H), 7.76 (dd, J=5.02, 3.01Hz, 1H), 8.15 (d, J=4.77 Hz, 1H), 8.71 (d, J=2.38 Hz, 1H), 9.07 (s, 1H),9.12 (d, J=2.13 Hz, 1H), 9.22 (d, J=1.51 Hz, 1H), 9.28 (s, 1H), 9.37 (d,J=0.88 Hz, 1H), 10.90 (s, 1H), 14.61 (brs, 1H); ESIMS found forC₂₆H₂₁N₇OS m/z 480.2 (M+1).

N-(5-(3-(4-(Thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide271

White solid (17.2 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm7.30-7.38 (m, 1H), 7.53 (d, J=7.78 Hz, 1H), 7.59-7.74 (m, 5H), 8.12(brs, 1H), 8.14 (brs, 2H), 8.74 (d, J=2.01 Hz, 1H), 9.12 (s, 1H), 9.28(brs, 1H), 9.29 (brs, 1H), 9.39 (d, J=1.00 Hz, 1H), 9.43 (brs, 1H),11.11 (brs, 1H), 14.60 (brs, 1H); ESIMS found for C₂₉H₁₉N₇OS m/z 514.0(M+1).

N-(5-(3-(4-(Thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide277

White solid (33.0 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.98(t, J=7.40 Hz, 3H), 1.71 (sxt, J=7.40 Hz, 2H), 2.43-2.48 (m, 2H), 7.34(t, J=7.78 Hz, 1H), 7.53 (d, J=7.65 Hz, 1H), 7.65 (d, J=7.53 Hz, 1H),7.77 (dd, J=5.02, 3.01 Hz, 1H), 8.15 (d, J=5.40 Hz, 1H), 8.70 (d, J=2.13Hz, 1H), 9.09 (s, 1H), 9.12 (s, 1H), 9.23 (s, 1H), 9.28 (brs, 1H), 9.38(d, J=1.00 Hz, 1H), 11.01 (brs, 1H), 14.64 (brs, 1H); ESIMS found forC₂₆H₂₁N₇OS m/z 480.0 (M+1).

N-(5-(3-(4-(Thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide280

White solid (43.0 mg, 0.09 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.81-1.93 (m, 1H), 1.96-2.08 (m, 1H), 2.14-2.25 (m, 2H), 2.27-2.40 (m,2H), 3.28-3.38 (m, 1H), 7.33 (t, J=7.78 Hz, 1H), 7.50 (d, J=7.78 Hz,1H), 7.65 (d, J=7.15 Hz, 1H), 7.74 (dd, J=5.02, 3.01 Hz, 1H), 8.14-8.20(m, 1H), 8.74 (brs, 1H), 8.82 (s, 1H), 9.01 (s, 2H), 9.05 (d, J=1.76 Hz,1H), 9.33 (s, 1H), 10.22 (s, 1H), 13.38 (brs, 1H); ESIMS found forC₂₇H₂₁N₇OS m/z 492.1 (M+1).

N-Benzyl-1-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine283

White solid (31.0 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 4.32(t, J=5.71 Hz, 2H), 4.47 (t, J=5.27 Hz, 2H), 7.34 (t, J=7.72 Hz, 1H),7.41-7.48 (m, 3H), 7.52 (d, J=7.28 Hz, 1H), 7.59 (dd, J=7.84, 1.69 Hz,2H), 7.65 (d, J=8.28 Hz, 1H), 7.72 (dd, J=5.02, 3.01 Hz, 1H), 8.12 (d,J=4.64 Hz, 1H), 8.80 (brs, 1H), 8.90 (d, J=1.76 Hz, 1H), 8.95 (s, 1H),9.13 (d, J=1.13 Hz, 1H), 9.36 (d, J=1.26 Hz, 1H), 9.47 (d, J=2.01 Hz,1H), 9.72-9.83 (m, 2H), 13.45 (brs, 1H), 14.58 (brs, 1H); ESIMS foundfor C₃₀H₂₃N₇S m/z 514.1 (M+1).

N-(5-(3-(4-(Furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide288

White solid (17.0 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.99(d, J=6.65 Hz, 6H), 2.11-2.22 (m, 1H), 2.35 (d, J=7.28 Hz, 2H), 7.32 (t,J=7.8 Hz, 1H), 7.37 (s, 1H), 7.49 (d, J=7.91 Hz, 1H), 7.55 (d, J=7.40Hz, 1H), 7.85 (s, 1H), 8.91 (s, 1H), 9.06 (s, 1H), 9.15 (s, 1H), 9.27(br. s., 2H), 9.38 (s, 1H), 11.01 (s, 1H), 14.64 (brs, 1H); ESIMS foundfor C₂₇H₂₃N₇O₂ m/z 478.2 (M+1).

N-((5-(3-(4-(Furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine292

White solid (92.4 mg, 0.21 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.29(t, J=7.15 Hz, 3H), 3.03-3.14 (m, 2H), 4.38-4.45 (m, 2H), 7.29-7.38 (m,2H), 7.50 (d, J=8.16 Hz, 1H), 7.55 (d, J=7.40 Hz, 1H), 7.87 (s, 1H),8.95 (s, 1H), 8.97 (s, 1H), 9.06 (s, 1H), 9.13 (s, 1H), 9.37 (s, 1H),9.41-9.49 (m, 2H), 9.50 (s, 1H), 14.65 (brs, 1H); ESIMS found forC₂₅H₂₁N₇O m/z 436.1 (M+1).

N-(5-(3-(4-(Furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide294

White solid (34.7 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.30(s, 9H), 7.30 (t, J=7.64 Hz, 1H), 7.38 (s, 1H), 7.46 (d, J=7.91 Hz, 1H),7.55 (d, J=7.28 Hz, 1H), 7.83 (s, 1H), 8.87-8.95 (m, 3H), 8.98 (s, 1H),9.04 (d, J=1.38 Hz, 1H), 9.32 (s, 1H), 9.64 (s, 1H), 13.35 (brs, 1H),14.38 (brs, 1H); ESIMS found for C₂₇H₂₃N₇O₂ m/z 478.1 (M+1).

N-(5-(3-(4-(Furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide295

White solid (26.4 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.20(d, J=6.90 Hz, 6H), 2.75 (spt, J=6.76 Hz, 2H), 7.32 (t, J=7.8 Hz, 1H),7.37 (d, J=1.25 Hz, 1H), 7.50 (d, J=7.78 Hz, 1H), 7.55 (d, J=7.03 Hz,1H), 7.85 (t, J=1.57 Hz, 1H), 8.91 (s, 1H), 9.08 (d, J=0.88 Hz, 1H),9.18 (d, J=2.01 Hz, 1H), 9.29 (s, 1H), 9.32 (d, J=1.88 Hz, 1H), 9.38 (d,J=1.00 Hz, 1H), 11.03 (s, 1H), 14.67 (brs, 1H); ESIMS found forC₂₆H₂₁N₇O₂ m/z 464.2 (M+1).

5-(3-(4-(Furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N-isopropylpyridin-3-amine298

White solid (32.5 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.26(d, J=6.27 Hz, 6H), 3.88-3.96 (m, 1H), 7.30-7.37 (m, 2H), 7.52 (d,J=7.91 Hz, 1H), 7.55 (d, J=7.53 Hz, 1H), 7.87 (s, 1H), 8.12 (d, J=2.13Hz, 1H), 8.34 (s, 1H), 8.70 (s, 1H), 8.92 (s, 1H), 9.08 (s, 1H), 9.36(d, J=0.88 Hz, 1H), 14.77 (brs, 1H); ESIMS found for C₂₅H₂₁N₇O m/z 436.2(M+1).

N-(5-(3-(4-(Furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide304

White solid (42.3 mg, 0.09 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.93(t, J=7.34 Hz, 3H), 1.38 (sxt, J=7.64 Hz, 2H), 1.65 (quin, J=7.50 Hz,2H), 2.42 (t, J=7.40 Hz, 2H), 7.30 (t, J=7.64 Hz, 1H), 7.39 (s, 1H),7.47 (d, J=7.65 Hz, 1H), 7.55 (d, J=7.91 Hz, 1H), 7.83 (t, J=1.69 Hz,1H), 8.83 (d, J=2.26 Hz, 1H), 8.88 (s, 1H), 8.97 (s, 2H), 9.05 (d,J=1.76 Hz, 1H), 9.33 (d, J=1.00 Hz, 1H), 10.36 (s, 1H), 13.34 (brs, 1H),14.39 (s, 1H); ESIMS found for C₂₇H₂₃N₇O₂ m/z 478.1 (M+1).

N-(5-(3-(4-(Furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide306

White solid (23.4 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.81-1.92 (m, 1H), 1.94-2.06 (m, 1H), 2.14-2.24 (m, 2H), 2.26-2.37 (m,2H), 3.30 (quin, J=8.04 Hz, 1H), 7.31 (t, J=7.8 Hz, 1H), 7.38 (s, 1H),7.48 (d, J=7.53 Hz, 1H), 7.55 (d, J=6.65 Hz, 1H), 7.84 (t, J=1.69 Hz,1H), 8.89 (s, 2H), 8.99 (s, 1H), 9.04 (s, 1H), 9.09 (d, J=1.88 Hz, 1H),9.34 (d, J=1.13 Hz, 1H), 10.28 (s, 1H), 13.36 (s, 1H), 14.41 (brs, 1H);ESIMS found for C₂₇H₂₁N₇O₂ m/z 476.1 (M+1).

1-Cyclopentyl-N-((5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine310

White solid (62.4 mg, 0.13 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.21-1.33 (m, 2H), 1.45-1.55 (m, 2H), 1.56-1.65 (m, 2H), 1.76-1.86 (m,2H), 2.26 (spt, J=7.88 Hz, 1H), 2.97-3.05 (m, 2H), 4.43 (d, J=5.02 Hz,2H), 7.33 (t, J=7.76 Hz, 1H), 7.36 (d, J=1.51 Hz, 1H), 7.50 (d, J=7.53Hz, 1H), 7.56 (d, J=7.40 Hz, 1H), 7.86 (t, J=1.69 Hz, 1H), 8.98 (s, 1H),9.03 (d, J=1.38 Hz, 1H), 9.15 (d, J=1.00 Hz, 1H), 9.17 (brs, 1H), 9.38(d, J=1.13 Hz, 1H), 9.40-9.48 (m, 2H), 9.54 (d, J=1.76 Hz, 1H), 14.70(brs, 1H); ESIMS found for C₂₉H₂₇N₇O m/z 490.1 (M+1).

N-(5-(3-(4-(Thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide313

White solid (22.8 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.17(t, J=7.59 Hz, 3H), 2.46 (q, J=7.64 Hz, 6H), 7.28 (dd, J=8.16, 3.14 Hz,1H), 7.31-7.35 (m, 1H), 7.48 (d, J=7.78 Hz, 1H), 7.64-7.70 (m, 2H), 8.19(d, J=2.64 Hz, 1H), 8.74 (d, J=1.88 Hz, 1H), 9.00 (s, 1H), 9.06 (d,J=1.38 Hz, 1H), 9.15 (s, 1H), 9.33 (s, 1H), 10.35 (s, 1H), 13.43 (brs,1H); ESIMS

found for C₂₅H₁₉N₇OS m/z 466.0 (M+1).

N,N-Dimethyl-5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine319

White solid (88.0 mg, 0.20 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 3.09(s, 6H), 7.24 (dd, J=5.08, 3.70 Hz, 1H), 7.32 (t, J=7.78 Hz, 1H), 7.48(d, J=7.78 Hz, 1H), 7.63 (dd, J=5.08, 0.82 Hz, 1H), 7.68 (d, J=7.53 Hz,1H), 7.78 (t, J=2.40 Hz, 1H), 8.17 (d, J=2.89 Hz, 1H), 8.21 (d, J=2.89Hz, 1H), 8.72 (d, J=1.51 Hz, 1H), 9.15 (s, 1H), 9.32 (d, J=1.13 Hz, 1H),13.43 (s, 1H), 14.36 (s, 1H); ESIMS found for C₂₄H₁₉N₇S m/z 438.0 (M+1).

N-(5-(3-(4-(Thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide320

White solid (33.1 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.32(s, 9H), 7.26-7.37 (m, 2H), 7.50 (d, J=7.65 Hz, 1H), 7.67 (d, J=7.65 Hz,1H), 7.72 (d, J=5.40 Hz, 1H), 8.22 (d, J=3.39 Hz, 1H), 9.15 (d, J=1.26Hz, 1H), 9.18 (brs, 1H), 9.22 (s, 1H), 9.30 (brs, 1H), 9.36 (d, J=1.13Hz, 1H), 10.17 (brs, 1H), 13.50 (s, 1H), 14.61 (brs, 1H); ESIMS foundfor C₂₇H₂₃N₇OS m/z 494.1 (M+1).

N-(5-(3-(4-(Thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide321

White solid (42.5 mg, 0.09 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.21(d, J=6.90 Hz, 6H), 2.77 (spt, J=6.68 Hz, 1H), 7.28-7.36 (m, 2H),7.47-7.52 (m, 1H), 7.63-7.69 (m, 1H), 7.76 (dd, J=5.02, 1.00 Hz, 1H),8.17-8.23 (m, 1H), 9.16 (dd, J=5.46, 1.82 Hz, 2H), 9.22 (d, J=1.25 Hz,1H), 9.37 (d, J=1.26 Hz, 2H), 11.05 (s, 1H), 14.64 (brs, 1H); ESIMSfound for C₂₆H₂₁N₇OS m/z 480.2 (M+1).

N,N-Dimethyl-1-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine325

White solid (10.1 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.82(d, J=4.14 Hz, 6H), 4.57 (d, J=4.27 Hz, 2H), 7.26-7.32 (m, 1H), 7.34 (d,J=7.64 Hz, 1H), 7.51 (d, J=7.91 Hz, 1H), 7.67 (d, J=7.78 Hz, 1H), 7.74(d, J=5.02 Hz, 1H), 8.21 (d, J=3.01 Hz, 1H), 9.01 (s, 1H), 9.03 (brs,1H), 9.27 (s, 1H), 9.38 (d, J=1.13 Hz, 1H), 9.49 (s, 1H), 10.93 (brs,1H), 14.65 (brs, 1H); ESIMS found for C₂₅H₂₁N₇S m/z 452.1 (M+1).

N-(5-(3-(4-(Thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide329

White solid (26.7 mg, 0.06 mmol). ¹H NMR (CD₃OD, 400 MHz) δ ppm 1.08 (t,J=7.40 Hz, 3H), 1.81 (sxt, J=7.38 Hz, 2H), 2.50 (t, J=7.40 Hz, 2H), 7.27(dd, J=5.02, 3.51 Hz, 1H), 7.43 (t, J=8.00 Hz, 1H), 7.53-7.66 (m, 3H),7.86 (d, J=2.64 Hz, 1H), 9.01 (d, J=13.80 Hz, 2H), 9.07-9.14 (m, 2H),9.19 (s, 1H); ESIMS found for C₂₆H₂₁N₇OS m/z 480.1 (M+1).

N-(5-(3-(4-(Thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide331

White solid (49.5 mg, 0.10 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm0.86-0.94 (m, 4H), 1.89 (quin, J=6.15 Hz, 1H), 7.27 (dd, J=5.02, 3.76Hz, 1H), 7.32 (t, J=7.80 Hz, 1H), 7.48 (d, J=7.65 Hz, 1H), 7.63 (dd,J=5.02, 0.88 Hz, 1H), 7.67 (d, J=7.40 Hz, 1H), 8.19 (dd, J=3.64 Hz,J=0.88 Hz, 1H), 8.74 (d, J=2.26 Hz, 1H), 8.97 (t, J=2.01 Hz, 1H), 9.06(d, J=1.76 Hz, 1H), 9.16 (s, 1H), 9.32 (d, J=1.13 Hz, 1H), 10.63 (s,1H), 13.42 (s, 1H), 14.38 (s, 1H); ESIMS found for C₂₆H₁₉N₇OS m/z 478.1(M+1).

5-(5-((3,3-Difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine337

White solid (59.7 mg, 0.12 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm2.21-2.31 (m, 2H), 2.76-2.83 (m, 2H), 2.93-3.03 (m, 2H), 3.84 (brs, 2H),7.28 (dd, J=5.02, 3.76 Hz, 1H), 7.32 (t, J=7.72 Hz, 1H), 7.49 (d, J=8.03Hz, 1H), 7.65-7.71 (m, 2H), 8.21 (d, J=2.64 Hz, 1H), 8.46 (s, 1H), 8.60(d, J=1.63 Hz, 1H), 9.23 (s, 1H), 9.32 (d, J=2.13 Hz, 1H), 9.34 (d,J=1.13 Hz, 1H), 13.44 (s, 1H), 14.37 (s, 1H); ESIMS found forC₂₇H₂₁F₂N₇S m/z 514.1 (M+1).

N-(5-(3-(4-(5-Fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide340

White solid (35.0 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.98(d, J=6.65 Hz, 6H), 2.14 (non, J=7.16 Hz, 1H), 2.31 (d, J=7.03 Hz, 2H),6.87 (dd, J=4.20, 2.20 Hz, 1H), 7.32 (t, J=7.76 Hz, 1H), 7.48 (d, J=7.91Hz, 1H), 7.66 (d, J=7.28 Hz, 1H), 7.79 (t, J=3.95 Hz, 1H), 8.96 (d,J=1.63 Hz, 1H), 9.08-9.13 (m, 2H), 9.15 (d, J=0.88 Hz, 1H), 9.36 (d,J=1.13 Hz, 1H), 10.62 (s, 1H), 13.50 (brs, 1H), 14.52 (brs, 1H); ESIMSfound for C₂₇H₂₂FN₇OS m/z 512.3 (M+1).

3-(4-(5-Fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine352

White solid (66.3 mg, 0.13 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.85-1.96 (m, 2H), 2.01-2.11 (m, 2H), 3.11-3.24 (m, 2H), 3.43-3.54 (m,2H), 4.67 (brs, 2H), 6.91 (brs, 1H), 7.32 (t, J=7.78 Hz, 1H), 7.51 (d,J=7.91 Hz, 1H), 7.65 (d, J=5.40 Hz, 1H), 7.82 (d, J=3.51 Hz, 1H),9.11-9.33 (m, 2H), 9.24 (s, 1H), 9.40 (s, 1H), 9.53 (brs, 1H), 11.49(brs, 1H), 14.79 (brs, 1H); ESIMS found for C₂₇H₂₂FN₇S m/z 496.1 (M+1).

N-(5-(3-(4-(5-Fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide358

White solid (69.1 mg, 0.14 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.79-1.93 (m, 1H), 1.95-2.07 (m, 1H), 2.14-2.26 (m, 2H), 2.27-2.38 (m,2H), 3.30-3.42 (m, 1H), 6.89 (dd, J=4.14, 2.13 Hz, 1H), 7.27-7.37 (m,1H), 7.48 (d, J=7.91 Hz, 1H), 7.58-7.68 (m, 1H), 7.83 (t, J=3.76 Hz,1H), 9.06-9.20 (m, 1H), 9.16 (brs, 2H), 9.26-9.34 (m, 1H), 9.36 (d,J=5.90 Hz, 1H), 10.75-10.96 (m, 1H), 13.54 (brs, 1H), 14.63 (brs, 1H);ESIMS found for C₂₇H₂₀FN₇OS m/z 510.1 (M+1).

3-Methyl-N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide366

White solid (19.2 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.98(d, J=6.65 Hz, 5H), 2.10-2.23 (m, 1H), 2.34 (d, J=7.15 Hz, 2H), 2.57 (s,3H), 6.99 (d, J=2.51 Hz, 1H), 7.29 (t, J=7.92 Hz, 1H), 7.45 (d, J=7.78Hz, 1H), 7.57 (d, J=7.15 Hz, 1H), 8.01 (d, J=3.64 Hz, 1H), 9.11 (d,J=1.88 Hz, 1H), 9.16 (d, J=1.63 Hz, 1H), 9.20 (s, 1H), 9.22 (d, J=1.00Hz, 1H), 9.36 (d, J=1.13 Hz, 1H), 10.97 (s, 1H), 14.62 (brs, 1H); ESIMSfound for C₂₈H₂₅N₇OS m/z 508.2 (M+1).

5-(3-(4-(5-Methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine367

White solid (35.9 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.57(s, 3H), 6.99 (dd, J=3.51, 1.13 Hz, 1H), 7.29 (t. J=7.76 Hz, 1H), 7.45(d, J=8.03 Hz, 1H), 7.58 (d, J=7.03 Hz, 1H), 7.99 (d, J=3.64 Hz, 1H),8.11 (d, J=2.26 Hz, 1H), 8.38 (t, J=1.88 Hz, 1H), 8.61 (s, 1H), 9.14 (d,J=1.13 Hz, 1H), 9.35 (d, J=1.25 Hz, 1H), 13.47 (brs, 1H) 14.61 (brs,1H); ESIMS found for C₂₃H₁₇N₇S m/z 424.0 (M+1).

N-(5-(3-(4-(5-Methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide373

White solid (21.3 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.17(d, J=6.90 Hz, 6H), 2.61 (s, 3H), 2.68 (sxt, J=6.80 Hz, 2H), 6.96 (dd,J=3.58, 1.07 Hz, 1H), 7.29 (t, J=7.76 Hz, 1H), 7.44 (d, J=7.65 Hz, 1H),7.61 (d, J=7.40 Hz, 1H), 7.94 (d, J=3.51 Hz, 1H), 8.85 (d, J=2.38 Hz,1H), 8.97 (t, J=2.20 Hz, 1H), 9.10 (d, J=2.01 Hz, 1H), 9.28 (s, 1H),9.32 (d, J=1.25 Hz, 1H), 10.28 (s, 1H), 13.40 (brs, 1H) 14.36 (s, 1H);ESIMS found for C₂₇H₂₃N₇OS m/z 494.1 (M+1).

3-(4-(5-Methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine379

White solid (26.6 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.31-1.45 (m, 1H), 1.66-1.77 (m, 2H), 1.80 (brs, 3H), 2.64 (s, 3H),2.90-3.02 (m, 2H), 3.42 (d, J=10.92 Hz, 2H), 4.53 (d, J=4.52 Hz, 2H),6.97 (dd, J=3.522 Hz, J=0.88 Hz, 1H), 7.30 (t, J=7.80 Hz, 1H), 7.46 (d,J=7.78 Hz, 1H), 7.60 (d, J=7.28 Hz, 1H), 7.96 (d, J=3.51 Hz, 1H), 9.02(d, J=9.66 Hz, 2H), 9.35 (s, 1H), 9.37 (d, J=1.00 Hz, 1H), 9.52 (d,J=1.76 Hz, 1H), 10.74 (brs, 1H), 13.48 (brs, 1H), 14.62 (brs, 1H); ESIMSfound for C₂₉H₂₇N₇S m/z 506.1 (M+1).

N-(5-(3-(4-(5-Methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide381

White solid (52.9 mg, 0.11 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.96(t, J=7.34 Hz, 3H), 1.67 (sxt, J=7.35 Hz, 2H), 2.39 (t, J=7.28 Hz, 2H),2.61 (s, 3H), 6.95 (d, J=2.64 Hz, 1H), 7.28 (t, J=7.8 Hz, 1H), 7.43 (d,J=7.78 Hz, 1H), 7.61 (d, J=7.53 Hz, 1H), 7.91 (d, J=3.51 Hz, 1H), 8.81(d, J=2.26 Hz, 1H), 8.96 (s, 1H), 9.10 (d, J=1.51 Hz, 1H), 9.29 (s, 1H),9.32 (s, 1H), 10.30 (s, 1H), 13.39 (brs, 1H); ESIMS found for C₂₇H₂₃N₇OSm/z 494.1 (M+1).

N-(5-(3-(4-(5-Methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide385

White solid (25.6 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.56-1.65 (m, 2H), 1.65-1.85 (m, 4H), 1.87-1.98 (m, 2H), 2.58 (s, 3H),2.85-2.94 (m, 1H), 6.97 (dd, J=3.52 Hz, J=1.00 Hz, 1H), 7.29 (t, J=7.92Hz, 1H), 7.44 (d, J=7.91 Hz, 1H), 7.59 (d, J=7.40 Hz, 1H), 7.98 (d,J=3.51 Hz, 1H), 8.98 (d, J=2.01 Hz, 1H), 9.08 (s, 1H), 9.13 (d, J=1.88Hz, 1H), 9.25 (s, 1H), 9.34 (d, J=1.13 Hz, 1H), 10.61 (s, 1H), 13.44(brs, 1H) 14.47 (s, 1H); ESIMS found for C₂₉H₂₅N₇OS m/z 520.1 (M+1).

N-(5-(3-(4-(5-Acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide392

White solid (9.1 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.98(d, J=6.65 Hz, 6H), 2.14 (non, J=6.16 Hz, 1H), 2.33 (d, J=7.15 Hz, 2H),2.60 (s, 3H), 7.36 (t, J=7.64 Hz, 1H), 7.59 (d, J=7.91 Hz, 1H), 7.81 (d,J=7.40 Hz, 1H), 8.07 (d, J=4.02 Hz, 1H), 8.29 (d, J=3.89 Hz, 1H), 9.05(s, 1H), 9.08-9.14 (m, 2H), 9.17 (brs, 1H), 9.36 (s, 1H), 10.66 (brs,1H), 13.58 (brs, 1H), 14.58 (brs, 1H); ESIMS found for C₂₉H₂₅N₇O₂S m/z536.1 (M+1).

1-(5-(2-(5-(Pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one394

White solid (72.3 mg, 0.17 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.66(s, 3H), 7.38 (t, J=7.76 Hz, 1H), 7.59 (d, J=7.78 Hz, 1H), 7.90 (d,J=7.65 Hz, 1H), 7.92-7.98 (m, 1H), 8.06 (d, J=3.89 Hz, 1H), 8.12 (d,J=3.89 Hz, 1H), 8.77 (d, J=4.27 Hz, 1H), 8.87 (d, J=7.78 Hz, 1H), 9.28(s, 1H), 9.37 (s, 1H), 9.54 (s, 1H), 13.60 (brs, 1H), 14.51 (s, 1H);ESIMS found for C₂₄H₁₆N₆OS m/z 437.0 (M+1).

N-(5-(3-(4-(5-Acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide400

White solid (15.3 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.59(s, 3H), 3.82 (s, 2H), 7.24-7.30 (m, 1H), 7.32-7.42 (m, 5H), 7.58 (d,J=7.78 Hz, 1H), 7.83 (d, J=7.65 Hz, 1H), 8.08 (d, J=4.02 Hz, 1H), 8.26(d, J=4.02 Hz, 1H), 9.17 (s, 1H), 9.20 (d, J=1.13 Hz, 1H), 9.22 (s, 2H),9.37 (d, J=1.13 Hz, 1H), 11.25 (s, 1H), 13.62 (brs, 1H), 14.64 (brs,1H); ESIMS found for C₃₂H₂₃N₇O₂S m/z 570.2 (M+1).

N-(5-(3-(4-(5-Acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide406

White solid (6.5 mg, 0.01 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.06(s, 9H), 2.31 (s, 2H), 2.60 (s, 3H), 7.38 (t, J=7.84 Hz, 1H), 7.60 (d,J=7.65 Hz, 1H), 7.83 (d, J=7.40 Hz, 1H), 8.05 (d, J=3.89 Hz, 1H), 8.29(d, J=3.39 Hz, 1H), 8.99 (brs, 1H), 9.03 (t, J=4.71 Hz, 1H), 9.10-9.17(m, 2H), 9.38 (s, 1H), 10.44 (brs, 1H), 13.60 (brs, 1H), 14.54 (s, 1H);ESIMS found for C₃₀H₂₇N₇O₂S m/z 550.2 (M+1).

N-(5-(3-(4-(5-Acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide412

White solid (51.9 mg, 0.09 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.20-1.37 (m, 3H), 1.39-1.52 (m, 2H), 1.67 (d, J=11.29 Hz, 1H),1.74-1.82 (m, 2H), 1.87 (d, J=13.30 Hz, 2H), 2.37-2.46 (m, 1H), 2.58 (s,3H), 7.37 (t, J=7.78 Hz, 1H), 7.59 (d, J=8.03 Hz, 1H), 7.81 (d, J=7.65Hz, 1H), 8.03 (d, J=4.14 Hz, 1H), 8.31 (d, J=3.89 Hz, 1H), 8.84-8.89 (m,2H), 9.02 (s, 1H), 9.05 (d, J=1.63 Hz, 1H), 9.34 (d, J=0.88 Hz, 1H),10.19 (s, 1H), 13.55 (s, 1H), 14.46 (s, 1H); ESIMS found for C₃₁H₂₇N₇O₂Sm/z 562.2 (M+1).

N-(3-Fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide421

White solid (42.4 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.66(s, 3H), 2.88 (s, 3H), 4.24 (d, J=6.15 Hz, 2H), 7.16-7.22 (m, 1H), 7.40(t, J=7.80 Hz, 1H), 7.60 (dd, J=12.30, 7.91 Hz, 2H), 7.68 (t, J=6.40 Hz,1H), 7.96-8.03 (m, 2H), 8.19-8.31 (m, 1H), 8.71 (d, J=1.13 Hz, 1H), 8.82(d, J=5.52 Hz, 1H), 9.07 (s, 1H), 9.38 (d, J=1.25 Hz, 1H), 14.57 (brs,1H); ESIMS found for C₂₇H₂₂FN₇O₂S m/z 528.1 (M+1).

N-(5-(3-(4-(3-Fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide424

White solid (35.0 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.31(s, 9H), 2.89 (s, 3H), 4.31 (d, J=5.77 Hz, 2H), 7.22 (d, J=9.29 Hz, 1H),7.43 (t, J=7.76 Hz, 1H), 7.63 (d, J=7.53 Hz, 1H), 7.67 (d, J=7.91 Hz,1H), 7.73 (t, J=6.02 Hz, 1H), 8.00 (s, 1H), 8.34 (d, J=11.29 Hz, 1H),9.08 (s, 1H), 9.23 (s, 1H), 9.34 (s, 2H), 9.38 (d, J=1.00 Hz, 1H), 10.28(s, 1H), 14.73 (brs, 1H); ESIMS found for C₃₁H₂₉FN₈O₃S m/z 613.2 (M+1).

N-(5-(3-(4-(3-Fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide427

White solid (12.8 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.90(s, 3H), 4.30 (d, J=6.02 Hz, 2H), 7.09 (d, J=8.41 Hz, 1H), 7.42 (t,J=7.78 Hz, 1H), 7.59-7.66 (m, 4H), 7.66-7.76 (m, 2H), 7.99 (brs, 1H),8.08 (d, J=1.26 Hz, 1H), 8.10 (s, 1H), 8.34-8.45 (m, 1H), 9.06 (d,J=0.88 Hz, 1H), 9.20 (s, 1H), 9.25 (brs, 1H), 9.27 (s, 1H), 9.38 (d,J=1.13 Hz, 1H), 10.96 (s, 1H), 14.58 (brs, 1H); ESIMS found forC₃₃H₂₅FN₈O₃S m/z 633.2 (M+1).

N-(5-(3-(4-(3-Fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide433

White solid (39.5 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm ¹H NMR(400 MHz, DMSO-d₆) δ 0.97 (t, J=7.34 Hz, 3H), 1.68 (sxt, J=7.33 Hz, 2H),2.43 (t, J=7.28 Hz, 2H), 2.89 (s, 3H), 4.32 (d, J=6.15 Hz, 2H),7.20-7.27 (m, 1H), 7.42 (t, J=7.78 Hz, 1H), 7.63 (dd, J=11.48, 7.72 Hz,2H), 7.72 (t, J=5.96 Hz, 1H), 8.01 (brs, 1H), 8.32 (d, J=2.26 Hz, 1H),9.03 (d, J=1.13 Hz, 1H), 9.10 (s, 2H), 9.15 (s, 1H), 9.37 (d, J=1.25 Hz,1H), 10.78 (brs, 1H), 14.60 (brs, 1H); ESIMS found for C₃₀H₂₇FN₈O₃S m/z599.1 (M+1).

N-(5-(3-(4-(3-Fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide435

White solid (48.2 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.78-1.91 (m, 1H), 1.93-2.06 (m, 1H), 2.12-2.22 (m, 2H), 2.23-2.35 (m,2H), 2.90 (s, 3H), 3.32 (quin, J=8.16 Hz, 1H), 4.33 (d, J=6.27 Hz, 2H),7.23 (d, J=8.66 Hz, 1H), 7.40 (t, J=7.68 Hz, 1H), 7.62 (d, J=7.65 Hz,2H), 7.72 (t, J=6.53 Hz, 1H), 8.00 (brs, 1H), 8.44 (brs, 1H), 8.89 (s,1H), 8.91 (s, 1H), 8.98 (s, 1H), 9.00 (d, J=1.38 Hz, 1H), 9.33 (d,J=1.13 Hz, 1H), 10.17 (s, 1H), 13.47 (brs, 1H), 14.41 (s, 1H); ESIMSfound for C₃₁H₂₇FN₈O₃S m/z 611.2 (M+1).

N-(3-(2-(5-(5-((Benzylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide439

White solid (27.5 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.93(s, 3H), 4.26-4.32 (m, 2H), 4.35 (d, J=6.40 Hz, 2H), 4.39-4.45 (m, 2H),7.24-7.30 (m, 1H), 7.38-7.49 (m, 4H), 7.55 (d, J=6.40 Hz, 2H), 7.63 (d,J=7.40 Hz, 2H), 7.77 (t, J=6.59 Hz, 1H), 7.95 (d, J=1.51 Hz, 1H), 8.80(s, 2H), 9.05 (s, 1H), 9.35 (d, J=1.13 Hz, 1H), 9.39 (s, 1H), 9.49-9.59(m, 2H), 14.52 (s, 1H); ESIMS found for C₃₄H₂₉FN₈O₂S m/z 633.2 (M+1).

N-(3-Fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide442

White solid (56.8 mg, 0.11 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 2.94(s, 3H), 4.35 (d, J=5.90 Hz, 2H), 7.27 (d, J=9.41 Hz, 1H), 7.42 (t,J=7.68 Hz, 1H), 7.63 (t, J=6.52 Hz, 2H), 7.75 (t, J=6.34 Hz, 1H), 7.97(s, 1H), 8.36-8.44 (m, 1H), 9.06 (d, J=1.00 Hz, 1H), 9.27 (s, 1H), 9.37(d, J=1.13 Hz, 1H), 9.50 (s, 2H), 14.56 (s, 1H); ESIMS found forC₂₅H₁₉FN₈O₂S m/z 515.1 (M+1).

N¹-(3-(2-(5-(5-((Ethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine448

White solid (31.6 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.28(t, J=5.04 Hz, 3H), 2.76-2.88 (m, 6H), 3.00-3.11 (m, 2H), 3.29 (brs,2H), 3.57 (brs, 2H), 4.39 (brs, 4H), 6.60 (d, J=11.44 Hz, 1H), 7.22(brs, 1H), 7.31-7.48 (m, 2H), 7.53 (d, J=6.15 Hz, 1H), 7.70 (d, J=7.03Hz, 1H), 9.02 (brs, 1H), 9.08 (brs, 1H), 9.19 (brs, 1H), 9.38 (s, 1H),9.53 (brs, 1H), 9.62 (brs, 2H), 10.61 (brs, 1H), 14.88 (brs, 1H); ESIMSfound for C₃₁H₃₂FN₉ m/z 550.2 (M+1).

N-(5-(3-(4-(3-((2-(Dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide450

White solid (30.1 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.28(s, 9H), 2.16-2.37 (m, 6H), 3.21-3.52 (m, 4H), 5.94 (brs, 1H), 6.46 (d,J=11.17 Hz, 1H), 7.31-7.40 (m, 2H), 7.47-7.52 (m, 2H), 7.55 (d, J=8.03Hz, 1H), 8.81 (s, 1H), 8.94-9.01 (m, 3H), 9.31 (s, 1H), 9.58 (s, 1H),13.37 (brs, 1H); ESIMS found for C₃₃H₃₄FN₉O m/z 592.3 (M+1).

N¹-(3-Fluoro-5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine454

White solid (39.4 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 1.19(d, J=6.27 Hz, 6H), 2.68-2.86 (m, 6H), 3.19-3.28 (m, 2H), 3.45-3.54 (m,2H), 3.63-3.73 (m, 1H), 5.86 (d, J=7.91 Hz, 1H), 6.54 (d, J=11.80 Hz,1H), 7.35 (t, J=7.65 Hz, 1H), 7.39-7.45 (m, 2H), 7.49 (d, J=7.65 Hz,1H), 7.55 (d, J=8.66 Hz, 1H), 7.66 (s, 1H), 8.01 (d, J=2.76 Hz, 1H),8.49 (d, J=1.63 Hz, 1H), 8.91 (s, 1H), 9.29 (d, J=1.13 Hz, 1H), 13.38(s, 1H), 14.33 (brs, 1H); ESIMS found for C₃₁H₃₂FN₉ m/z 550.2 (M+1).

N-(5-(3-(4-(3-((2-(Dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide460

White solid (50.0 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm 0.92(t, J=7.28 Hz, 3H), 1.37 (sxt, J=7.76 Hz, 2H), 1.62 (quin, J=7.16 Hz,2H), 2.39 (t, J=7.34 Hz, 2H), 2.59-2.83 (m, 5H), 3.43-3.53 (m, 2H),6.17-6.32 (m, 1H), 6.53 (d, J=11.67 Hz, 1H), 7.36 (t, J=7.65 Hz, 1H),7.41-7.53 (m, 3H), 7.56 (d, J=7.91 Hz, 1H), 8.82-8.88 (m, 2H), 8.97 (d,J=1.63 Hz, 1H), 9.00 (s, 1H), 9.32 (s, 1H), 10.24 (s, 1H), 13.39 (s,1H), 14.37 (brs, 1H); ESIMS found for C₃₃H₃₄FN₉O m/z 592.2 (M+1).

N¹-(3-(2-(5-(5-(((Cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine466

White solid (76.2 mg, 0.13 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δ ppm1.21-1.32 (m, 2H), 1.46-1.65 (m, 5H), 1.74-1.85 (m, 2H), 2.25 (spt,J=7.68 Hz, 2H), 2.82 (brs, 3H), 2.83 (brs, 3H), 2.94-3.02 (m, 2H),3.26-3.33 (m, 2H), 3.58 (t, J=6.46 Hz, 2H), 4.40 (brs, 2H), 6.60 (d,J=11.54 Hz, 1H), 7.26 (d, J=1.76 Hz, 1H), 7.38-7.48 (m, 2H), 7.53 (d,J=7.28 Hz, 1H), 7.66 (d, J=7.65 Hz, 1H), 8.99 (brs, 1H), 9.03 (d, J=2.13Hz, 1H), 9.15 (s, 1H), 9.38 (s, 1H), 9.39-9.47 (m, 2H), 9.49 (s, 1H),10.52 (brs, 1H), 14.76 (brs, 1H); ESIMS found for C₃₅H₃₈FN₉ m/z 604.3(M+1).

3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridine937

White solid (40.0 mg, 0.10 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 1.69(qd, J=12.40, 3.98 Hz, 2H), 2.01 (br d, J=12.35 Hz, 2H), 2.65-2.75 (m,2H), 2.86-2.96 (m, 1H), 3.12 (br d, J=11.80 Hz, 2H), 7.26 (td, J=8.37,2.20 Hz, 1H), 7.34 (t, J=7.82 Hz, 1H), 7.58 (dd, J=13.86, 7.55 Hz, 3H),8.10 (br d, J=7.96 Hz, 1H), 8.29 (s, 1H), 8.44 (br d, J=10.70 Hz, 1H),9.09 (d, J=1.10 Hz, 1H); ESIMS found for C₂₄H₂₁FN₆ m/z 413.2 (M+1).

3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine938

Off-white solid (190.0 mg, 0.44 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm2.61 (br s, 2H), 3.06 (t, J=5.63 Hz, 2H), 3.52 (br d, J=2.74 Hz, 2H),6.93 (br s, 1H), 7.26 (td, J=8.51, 2.20 Hz, 1H), 7.36 (t, J=7.68 Hz,1H), 7.53-7.59 (m, 2H), 7.61 (d, J=7.41 Hz, 1H), 8.07 (br d, J=7.14 Hz,1H), 8.50 (br s, 1H), 8.52 (s, 1H), 9.12 (d, J=1.37 Hz, 1H); ESIMS foundfor C₂₄H₁₉FN₆ m/z 411.1 (M+1).

3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine939

Yellow solid (4.5 mg, 0.01 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 7.30(td, J=8.23, 2.47 Hz, 1H), 7.37 (t, J=7.68 Hz, 1H), 7.55-7.65 (m, 3H),8.01-8.12 (m, 2H), 8.22 (br s, 1H), 8.58-8.66 (m, 2H), 9.15 (d, J=1.10Hz, 1H), 13.11 (br s, 1H), 13.37 (br s, 1H), 14.16 (br s, 1H); ESIMSfound for C₂₂H₁₄FN₇ m/z 396.1 (M+1).

3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine940

Yellow solid (2.3 mg, 0.006 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 3.94(s, 3H), 7.31 (br t, J=8.51 Hz, 1H), 7.37 (t, J=7.82 Hz, 1H), 7.55-7.67(m, 3H), 7.95 (s, 1H), 8.07 (d, J=7.96 Hz, 1H), 8.19 (s, 1H), 8.57-8.64(m, 2H), 9.14 (d, J=1.10 Hz, 1H), 13.35 (br s, 1H), 14.15 (br s, 1H);ESIMS found for C₂₃H₁₆FN₇ m/z 410.1 (M+1).

5-(1,2-Dimethyl-1H-imidazol-5-yl)-3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine941

Brown solid (8.7 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 2.42(s, 3H), 3.85 (s, 3H), 7.22-7.31 (m, 2H), 7.37 (t, J=7.82 Hz, 2H),7.53-7.63 (m, 3H), 8.09 (d, J=7.96 Hz, 1H), 8.40 (br d, J=11.25 Hz, 1H),8.64 (s, 1H), 9.24 (d, J=1.10 Hz, 1H), 13.38 (s, 1H), 14.27 (s, 1H);ESIMS found for C₂₄H₁₈FN₇ m/z 424.2 (M+1).

1-(6-(3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine942

Brown solid (5.9 mg, 0.012 mmol, 12.02% yield). ¹H NMR (DMSO-d₆, 500MHz) δ ppm 3.66-3.75 (m, 2H), 3.94 (dt, J=12.97, 6.55 Hz, 1H), 4.23 (brt, J=7.41 Hz, 2H), 7.32 (td, J=8.51, 2.20 Hz, 1H), 7.37 (t, J=7.82 Hz,1H), 7.49 (br d, J=7.14 Hz, 1H), 7.55-7.65 (m, 2H), 7.88 (s, 1H), 8.00(br d, J=10.98 Hz, 1H), 8.08 (br d, J=6.59 Hz, 1H), 8.83 (s, 1H), 9.19(s, 1H), 9.25 (d, J=0.82 Hz, 1H), 13.36 (br s, 2H); ESIMS found forC₂₆H₂₀FN₉ m/z 478.2 (M+H).

5-(5-(Cyclohexyloxy)pyridin-3-yl)-3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine943

Off-white solid (57 mg, 0.102 mmol, 17.22% yield). ¹H NMR (DMSO-d₆, 500MHz) δ ppm 1.28-1.37 (m, 1H), 1.42 (dtd, J=13.21, 9.86, 9.86, 3.29 Hz,2H), 1.50-1.62 (m, 3H), 1.70-181 (m, 2H), 1.94-2.05 (m, 2H), 4.54-4.63(m, 1H), 7.25 (td, J=8.44, 2.33 Hz, 1H), 7.38 (t, J=7.82 Hz, 1H), 7.60(dd, J=15.37, 7.68 Hz, 3H), 7.96-8.02 (m, 1H), 8.18 (d, J=7.68 Hz, 1H),8.36 (d, J=2.74 Hz, 1H), 8.42 (br d, J=11.25 Hz, 1H), 8.91 (d, J=1.65Hz, 1H), 8.99 (s, 1H), 9.31 (d, J=1.10 Hz, 1H), 13.44 (br s, 1H), 14.35(br s, 1H); ESIMS found for C₃₀H₂₅FN₆O m/z 505.2 (M+1).

3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine944

White solid (66 mg, 0.131 mmol, 49.2% yield). ¹H NMR (DMSO-d₆, 500 MHz)δ ppm 1.85-1.97 (m, 2H), 2.11-2.21 (m, 2H), 3.10 (ddd, J=12.49, 8.51,3.70 Hz, 2H), 3.25-3.32 (m, 2H), 4.89 (dt, J=7.27, 3.77 Hz, 1H), 7.29(td, J=8.37, 2.20 Hz, 1H), 7.39 (t, J=7.82 Hz, 1H), 7.56-7.66 (m, 3H),8.07 (t, J=2.20 Hz, 1H), 8.18 (br d, J=7.41 Hz, 1H), 8.41-8.51 (m, 2H),8.97 (d, J=1.37 Hz, 1H), 9.01 (s, 1H), 9.31 (d, J=1.37 Hz, 1H), 13.45(br s, 1H); ESIMS found for C₂₉H₂₄FN₇O m/z 506.2 (M+1).

N-(5-(3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide945

Brown solid (18.1 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm1.39-1.52 (m, 3H), 1.88 (br d, J=12.90 Hz, 2H), 2.05-2.16 (m, 1H), 2.40(d, J=6.86 Hz, 2H), 2.85-2.97 (m, 3H), 7.26 (td, J=8.37, 2.74 Hz, 1H),7.39 (t, J=7.82 Hz, 1H), 7.57-7.66 (m, 3H), 8.19 (br d, J=6.31 Hz, 1H),8.36 (br d, J=9.33 Hz, 1H), 8.44 (br d, J=11.25 Hz, 1H), 8.60 (br d,J=11.80 Hz, 1H), 8.82 (s, 1H), 8.89 (br s, 1H), 8.99 (s, 2H), 9.31 (d,J=1.10 Hz, 1H), 10.38 (s, 1H), 13.44 (br s, 1H), 14.39 (s, 1H); ESIMSfound for C₃₁H₂₇FN₈O m/z 547.3 (M+1).

3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine 946

Yellow solid (8 mg, 0.015 mmol, 35.8% yield). ¹H NMR (DMSO-d₆, 500 MHz)δ ppm 1.70 (dt, J=6.72, 3.22 Hz, 4H), 2.54-2.60 (m, 4H), 2.88 (t, J=5.76Hz, 2H), 4.27 (t, J=5.76 Hz, 2H), 7.26 (td, J=8.44, 2.33 Hz, 1H), 7.38(t, J=7.82 Hz, 1H), 7.56-7.65 (m, 3H), 7.99-8.05 (m, 1H), 8.17 (br d,J=6.59 Hz, 1H), 8.36 (d, J=2.74 Hz, 1H), 8.42 (br d, J=10.43 Hz, 1H),8.93 (d, J=1.65 Hz, 1H), 8.99 (s, 1H), 9.30 (d, J=1.10 Hz, 1H), 13.41(brs, 1H), 14.33 (brs, 1H); ESIMS found for C₃₀H₂₆FN₇O m/z 520.2 (M+1).

2-((5-(3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine947

Brown solid (29.1 mg, 0.059 mmol, 50.1% yield). ¹H NMR (DMSO-d₆, 500MHz) δ ppm 2.32 (s, 6H), 2.79 (br t, J=5.49 Hz, 2H), 4.28 (t, J=5.63 Hz,2H), 7.26 (td, J=8.37, 2.74 Hz, 1H), 7.38 (t, J=7.82 Hz, 1H), 7.60 (dd,J=12.76, 7.27 Hz, 3H), 7.99-8.05 (m, 1H), 8.17 (d, J=7.68 Hz, 1H), 8.37(d, J=2.74 Hz, 1H), 8.41 (br d, J=11.25 Hz, 1H), 8.94 (d, J=1.37 Hz,1H), 9.00 (s, 1H), 9.31 (d, J=0.82 Hz, 1H), 13.42 (br s, 1H); ESIMSfound for C₂₈H₂₄FN₇O m/z 494.2 (M+1).

3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine948

Yellow solid (31.2 mg, 0.07 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 3.96(s, 3H), 7.28 (td, J=8.51, 2.47 Hz, 1H), 7.38 (t, J=7.68 Hz, 1H),7.56-7.65 (m, 3H), 8.00-8.05 (m, 1H), 8.15 (br d, J=6.86 Hz, 1H), 8.37(d, J=2.74 Hz, 1H), 8.43 (br d, J=11.80 Hz, 1H), 8.93 (d, J=1.65 Hz,1H), 9.00 (s, 1H), 9.31 (s, 1H), 13.41 (br s, 1H), 14.33 (brs, 1H);ESIMS found for C₂₅H₁₇FN₆O m/z 437.2 (M+1).

5-(3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol949

Brown solid (17.7 mg, 0.042 mmol, 31.2% yield). ¹H NMR (DMSO-d₆, 500MHz) δ ppm 7.28 (td, J=8.51, 2.47 Hz, 1H), 7.38 (t, J=7.82 Hz, 1H),7.55-7.66 (m, 3H), 7.91 (t, J=2.20 Hz, 1H), 8.16-8.23 (m, 2H), 8.43 (brd, J=11.25 Hz, 1H), 8.79 (d, J=1.65 Hz, 1H), 8.98 (s, 1H), 9.30 (d,J=1.37 Hz, 1H), 10.09 (br s, 1H), 13.44 (br s, 1H), 14.13 (br s, 1H);ESIMS found for C₂₄H₁₅FN₆O m/z 423.2 (M+1).

5-(5-(Benzyloxy)pyridin-3-yl)-3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine950

Cream colored solid (110 mg, 0.204 mmol, 68.0% yield). ¹H NMR (DMSO-d₆,500 MHz) δ ppm 5.32 (s, 2H), 7.07-7.16 (m, 1H), 7.34-7.41 (m, 2H),7.42-7.49 (m, 2H), 7.55 (d, J=7.14 Hz, 2H), 7.56-7.64 (m, 3H), 8.07-8.13(m, 1H), 8.18 (br d, J=7.41 Hz, 1H), 8.40 (br d, J=11.25 Hz, 1H), 8.45(d, J=2.74 Hz, 1H), 8.97 (d, J=1.37 Hz, 1H), 9.02 (s, 1H), 9.32 (d,J=1.10 Hz, 1H), 13.44 (br s, 1H), 14.35 (br s, 1H); ESIMS found forC₃₁H₂₁FN₆O m/z 513.2 (M+1).

2-Cyclohexyl-N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide951

White solid (24 mg, 0.042 mmol, 58.5% yield). ¹H NMR (DMSO-d₆, 500 MHz)δ ppm 0.96-1.07 (m, 2H), 1.12-1.33 (m, 3H), 1.63 (br d, J=12.35 Hz, 1H),1.69 (br d, J=12.90 Hz, 2H), 1.75 (br d, J=10.98 Hz, 2H), 1.83 (ddt,J=14.48, 7.27, 3.67, 3.67 Hz, 1H), 2.29 (d, J=6.86 Hz, 2H), 7.24 (td,J=8.23, 2.47 Hz, 1H), 7.38 (t, J=7.68 Hz, 1H), 7.55-7.67 (m, 3H), 8.19(br d, J=7.68 Hz, 1H), 8.42 (br d, J=11.80 Hz, 1H), 8.79 (d, J=2.20 Hz,1H), 8.90 (s, 1H), 8.95-9.01 (m, 2H), 9.32 (d, J=1.10 Hz, 1H), 10.23 (s,1H), 13.44 (br s, 1H), 14.36 (br s, 1H); ESIMS found for C₃₂H₂₈FN₇O m/z546.2 (M+1).

3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine952

Off-white solid (80.0 mg, 0.19 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm7.32 (br t, J=8.51 Hz, 1H), 7.39 (t, J=7.68 Hz, 1H), 7.56-7.68 (m, 3H),8.06-8.15 (m, 3H), 8.56 (br d, J=11.53 Hz, 1H), 8.74 (br d, J=5.49 Hz,2H), 9.16 (s, 1H), 9.32 (s, 1H), 13.45 (s, 1H), 14.39 (s, 1H); ESIMSfound for C₂₄H₁₅FN₆ m/z 407.1 (M+1).

3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine953

Pink solid (47 mg, 0.110 mmol, 33.7% yield). ¹H NMR (DMSO-d₆, 500 MHz) δppm ¹H NMR (499 MHz, DMSO-d₆) δ ppm 7.30 (td, J=8.51, 2.20 Hz, 1H), 7.38(t, J=7.68 Hz, 1H), 7.44 (ddd, J=7.41, 4.80, 0.96 Hz, 1H), 7.55-7.69 (m,3H), 7.96 (td, J=7.75, 1.78 Hz, 1H), 8.22 (br d, J=7.68 Hz, 1H), 8.39(br d, J=10.70 Hz, 1H), 8.45 (d, J=7.96 Hz, 1H), 8.75 (d, J=4.12 Hz,1H), 9.26 (d, J=1.10 Hz, 1H), 9.63 (s, 1H), 13.42 (br s, 1H), 14.32 (brs, 1H); ESIMS found for C₂₄H₁₅FN₆ m/z 407.1 (M+1).

3-(4-(3-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridine954

Cream colored solid (53 mg, 0.130 mmol, 65.9% yield). ¹H NMR (DMSO-d₆,500 MHz) δ ppm 7.29 (td, J=8.51, 2.47 Hz, 1H), 7.39 (t, J=7.68 Hz, 1H),7.55-7.69 (m, 3H), 8.20 (d, J=7.96 Hz, 1H), 8.39 (br d, J=11.25 Hz, 1H),8.70 (d, J=2.47 Hz, 1H), 8.78 (s, 1H), 9.32 (d, J=1.10 Hz, 1H), 9.61 (brs, 1H), 9.61 (d, J=1.10 Hz, 1H), 13.46 (br s, 1H), 14.42 (br s, 1H);ESIMS found for C₂₃H₁₄FN₇ m/z 408.1 (M+1).

N-(5-(3-(4-(3-(2-(Dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide1262

Orange solid (10.2 mg, 0.017 mmol, 15.94% yield). ¹H NMR (DMSO-d₆, 500MHz) δ ppm 0.97 (d, J=6.59 Hz, 6H), 2.07-2.16 (m, 7H), 2.24-2.30 (m,4H), 4.17 (br t, J=5.90 Hz, 2H), 6.88 (br d, J=10.70 Hz, 1H), 7.37 (t,J=7.68 Hz, 1H), 7.58 (d, J=7.41 Hz, 1H), 7.63 (d, J=7.68 Hz, 1H), 7.85(s, 1H), 7.89 (br d, J=10.43 Hz, 1H), 8.81-8.86 (m, 2H), 8.92 (d, J=1.92Hz, 1H), 8.95 (s, 1H), 9.32 (d, J=1.10 Hz, 1H), 10.22 (s, 1H), 13.44 (brs, 1H), 14.38 (br s, 1H); ESIMS found for C₃₃H₃₃FN₈O₂ m/z 593.3 (M+1).

N-(5-(3-(4-(3-Fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide1306

Yellow solid (12.3 mg, 0.020 mmol, 53.7% yield). ¹H NMR (DMSO-d₆, 500MHz) δ ppm 0.90-1.02 (m, 10H), 1.87 (br s, 1H), 1.99 (br s, 1H),2.08-2.17 (m, 2H), 2.20-2.26 (m, 1H), 2.28 (d, J=7.14 Hz, 2H), 3.66 (brd, J=4.67 Hz, 2H), 4.46-4.53 (m, 2H), 6.98-7.05 (m, 1H), 7.39 (t, J=7.68Hz, 1H), 7.58-7.66 (m, 2H), 7.91 (br s, 1H), 7.98 (br d, J=9.61 Hz, 1H),8.85-8.92 (m, 2H), 8.95-9.02 (m, 2H), 9.33 (d, J=1.37 Hz, 1H), 10.25 (s,1H), 13.47 (s, 1H), 14.41 (s, 1H); ESIMS found for C₃₅H₃₅FN₈O₂ m/z 619.3(M+1).

N-(5-(3-(4-(3-Fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide1350

Yellow solid (34.2 mg, 0.066 mmol, 83% yield). ¹H NMR (DMSO-d₆, 500 MHz)δ ppm 0.98 (d, J=6.59 Hz, 6H), 2.13 (dquin, J=13.62, 6.75, 6.75, 6.75,6.75 Hz, 1H), 2.28 (d, J=7.14 Hz, 2H), 6.63 (dt, J=10.50, 2.16 Hz, 1H),7.36 (t, J=7.68 Hz, 1H), 7.53 (br d, J=7.41 Hz, 1H), 7.57 (br d, J=7.68Hz, 1H), 7.66 (s, 1H), 7.79 (br d, J=10.43 Hz, 1H), 8.85 (br d, J=11.53Hz, 2H), 9.01 (s, 2H), 9.32 (s, 1H), 10.01 (s, 1H), 10.18 (s, 1H), 13.40(s, 1H), 14.36 (s, 1H); ESIMS found for C₂₉H₂₄FN₇O₂ m/z 522.2 (M+1).

N-(5-(3-(4-(3-Fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide1394

Yellow solid (31.3 mg, 0.058 mmol, 71.0% yield). ¹H NMR (DMSO-d₆, 500MHz) δ ppm 0.98 (d, J=6.59 Hz, 6H), 2.13 (dquin, J=13.70, 6.80, 6.80,6.80, 6.80 Hz, 1H), 2.28 (d, J=7.14 Hz, 2H), 3.91 (s, 3H), 6.88 (dt,J=10.70, 2.20 Hz, 1H), 7.37 (t, J=7.82 Hz, 1H), 7.58 (br d, J=7.68 Hz,1H), 7.64 (br d, J=7.41 Hz, 1H), 7.84 (br d, J=10.98 Hz, 1H), 8.03 (brs, 1H), 8.83 (d, J=2.47 Hz, 1H), 8.88 (br s, 1H), 8.98 (d, J=1.65 Hz,2H), 9.32 (d, J=1.10 Hz, 1H), 10.22 (s, 1H), 13.43 (brs, 1H), 14.37(brs, 1H); ESIMS found for C₃₀H₂₆FN₇O₂ m/z 536.3 (M+1).

2-(Dimethylamino)-N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide1437

Orange solid (18.7 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 2.37(s, 6H), 3.23 (br s, 2H), 7.25 (td, J=8.30, 2.61 Hz, 1H), 7.39 (t,J=7.68 Hz, 1H), 7.57-7.66 (m, 3H), 8.19 (d, J=7.96 Hz, 1H), 8.40-8.47(m, 1H), 8.87 (d, J=2.20 Hz, 1H), 8.91 (t, J=2.20 Hz, 1H), 8.99 (d,J=1.10 Hz, 1H), 9.01 (d, J=1.92 Hz, 1H), 9.32 (d, J=1.37 Hz, 1H), 10.15(br s, 1H), 13.43 (s, 1H), 14.36 (br s, 1H); ESIMS found for C₂₈H₂₃FN₈Om/z 507.1 (M+1).

Example 2

The screening assay for Wnt activity is described as follows. Reportercell lines can be generated by stably transducing cancer cell lines(e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells)with a lentiviral construct that includes a Wnt-responsive promoterdriving expression of the firefly luciferase gene.

SW480 colon carcinoma cells were transduced with a lentiviral vectorexpressing luciferase with a human Sp5 promoter consisting of a sequenceof eight TCF/LEF binding sites. SW480 cells stably expressing theSp5-Luc reporter gene and a hygromycin resistance gene were selected bytreatment with 150 μg/ml of hygromycin for 7 days. These stablytransduced SW480 cells were expanded in cell culture and used for allfurther screening activities. For Sp5-Luc reporter gene assays, thecells were plated at 10,000 cells/well in 96-well plates with growthmedium containing 10% fetal calf serum and incubated overnight at 37° C.and 5% CO₂. Each compound was dissolved in DMSO as a 10 mM stock instandard j-vials and used to prepare compound source plates indose-response format with 3-fold serial dilutions and a 10 mM topconcentration. Compound transfer from serially diluted source plates toassay plates containing the cells was accomplished using a pintool(Multimek 96, Beckman equipped with V&P Scientific FP1S50H pins) basedliquid handling protocol. This protocol used a slotted pin to transfer50 nl of compound from a source plate well to an assay plate wellcontaining 50 μl of cells in growth medium. The 1000-fold dilutionresulted in a final DMSO concentration of 0.1% on the cells in eachwell. Control wells received 50 nl of DMSO treatment for normalizationand calculating IC₅₀ values. The treated cells were incubated at 37° C.and 5% CO₂ for an additional forty-two hours. Following incubation, thegrowth medium was removed and 50 μl of BrightGlo luminescence reagent(Promega) was added to each well of the 96-well assay plates. The plateswere placed on an orbital shaker for 5 min and then luminescence wasquantified on the Victor3 (Perkin Elmer) plate reader. Readings werenormalized to DMSO only treated cells, and normalized activities wereutilized for IC₅₀ calculations using the dose-response log (inhibitor)vs. response-variable slope (four parameters) nonlinear regressionfeature available in GraphPad Prism 5.0 or 6.0. Table 2 shows themeasured activity for selected compounds of Formula I as describedherein.

TABLE 2 Compound IC₅₀ (μM) 1 0.0439 7 0.0424 13 0.0191 20 0.0744 250.0873 28 0.0908 34 0.0312 40 0.2869 46 0.0489 52 0.1225 55 0.0195 610.0812 68 0.1642 73 0.1233 82 0.0045 87 0.0454 90 0.0139 93 0.5337 1010.1834 109 0.0425 121 >10 126 >10 136 0.1773 141 0.4111 148 0.1770 1540.5964 157 0.0972 169 0.0283 175 0.0769 181 0.0871 184 0.0551 190 0.0535196 0.7454 202 0.0632 211 0.0968 217 0.3554 223 2.186 229 0.6284 2340.7976 238 0.0077 244 0.2109 250 0.1832 256 0.0956 265 0.0194 268 0.0761269 0.0042 271 0.0538 277 0.0435 280 0.0062 283 0.0309 288 0.0068 2920.0296 294 0.0486 295 0.0393 298 0.0129 304 0.1449 306 0.0168 310 0.0588313 0.1263 319 0.0779 320 0.0566 321 0.0163 325 0.0267 329 0.0560 3310.0172 337 0.0908 340 0.0173 352 0.0305 358 0.0116 366 0.0311 367 0.0035373 0.0326 379 0.3590 381 0.0215 385 0.0331 392 0.0321 394 0.0443 4000.0423 406 0.2471 412 0.1497 421 0.0100 424 0.0199 427 0.1721 433 0.0285436 0.0258 439 0.0401 442 0.0260 448 0.6713 450 0.1594 454 0.0516 4600.1824 466 0.4663 937 3.165 938 0.145 939 0.025 940 0.046 941 0.334 9420.079 943 0.560 944 1.205 945 >10 946 0.580 947 0.463 948 0.033 9490.029 950 0.165 951 0.115 952 0.053 953 0.250 954 0.045 1262 0.747 13061.372 1350 >10 1394 0.183 1437 0.155

Example 3

The above synthesized compounds were screened using primary humanmesenchymal stem cells (hMSCs) to determine their ability to inducechondrogenesis (process by which cartilage is developed).

Human Mesenchymal Stem Cell Culture:

Primary human mesenchymal stem cells (hMSCs) were purchased from Lonza(Walkersville, Md.) and expanded in Mesenchymal Stem Cell Growth Media(Lonza). Cells between passage 3 and 6 were used for the experiments.

Compound Screening:

Each compound was dissolved in DMSO as a 10 mM stock and used to preparecompound source plates. Serial dilution (1:3, 6-point dose-responsecurves from 2700 nM to 10 nM) and compound transfer was performed usingthe ECHO 550 (Labcyte, Sunnyvale, Calif.) into 96-well clear bottomassay plates (Greiner Bio-One) with appropriate DMSO backfill for afinal DMSO concentration of 0.03%. hMSCs were plated at 20,000cells/well in 250 μL/well Incomplete Chondrogenic Induction Medium(Lonza; DMEM, dexamethasone, ascorbate, insulin-transferrin-selenium[ITSsupplement], gentamycin-amphotericin [GA-1000], sodium pyruvate, prolineand L-glutamine) TGF-β3 (10 ng/mL) was used as a positive control fordifferentiation while negative control wells were treated with 75 nLDMSO for normalization and calculating EC₅₀ values. Cells were incubatedat 37° C. and 5% CO₂ for 6 days. To image chondrogenic nodules, thecells were fixed using 4% formaldehyde (Electron Microscopy Sciences),and stained with 2 μg/mL Rhodamine B (Sigma-Aldrich) and 20 μM Nile Red(Sigma-Aldrich) [Johnson K., et. al, A Stem Cell-Based Approach toCartilage Repair, Science, (2012), 336(6082), 717-721]. The nodulesimaged (4 images per well at 4× magnification) by excitation at 531 nmand emission at 625 nm and quantified using the CellInsight CX5 (ThermoScientific). Number of nodules in each well was normalized to theaverage of 3 DMSO treated wells on the same plate using Excel (MicrosoftInc.). The normalized averages (fold change over DMSO) of 3 replicatewells for each compound concentration were calculated. Due to solubilitylimitations of some of the compounds, curve fitting was incompleteleading to inaccurate EC₅₀ determinations.

Using TGF-β3 as a positive control, the concentration of test compoundsrequired to induce equivalent levels of chondrogenesis is reported. Inaddition, the maximum activity of each compound and the respective dosethat each compound reached maximum chondrogenesis activity is reported.Table 3 shows the activity of selected compounds as provided herein.

TABLE 3 Conc Conc Max. (nM) of (nM) of Activity as 100% Max. % TGF-β3TGF-β3 Compound activity activity activity 13 300 100 311.4 34 2700 N/A28.4 55 900 300 105.2 82 30 100 92.9 169 900 N/A 60.3 184 30 N/A 26.7211 2700 N/A 37.9 238 100  30 80.5 269 900  10 66.3 288 10 N/A 58.0 331300 N/A 66.8 367 30  30 107.3 392 2700 N/A 29.4 421 100  30 81.8 454 300300 235.2 939 30  30 70.0

Example 4

The above synthesized compounds were screened using primary humanfibroblasts (derived from IPF patients) treated with TGF-β1 to determinetheir ability to inhibit the fibrotic process.

Human Fibroblast Cell Culture:

Primary human fibroblasts derived from IPF patients (LL29 cells)[¹Xiaoqiu Liu, et. al., “Fibrotic Lung Fibroblasts Show BluntedInhibition by cAMP Due to Deficient cAMP Response Element-BindingProtein Phosphorylation”, Journal of Pharmacology and ExperimentalTherapeutics (2005), 315(2), 678-687; ²Watts, K. L., et. al., “RhoAsignaling modulates cyclin D1 expression in human lung fibroblasts;implications for idiopathic pulmonary fibrosis”, Respiratory Research(2006), 7(1), 88] were obtained from American Type Culture Collection(ATCC) and expanded in F12 medium supplemented with 15% Fetal BovineSerum and Penicillin/Streptomycin.

Compound Screening:

Each compound was dissolved in DMSO as a 10 mM stock and used to preparecompound source plates. Serial dilution (1:2, 11-point dose-responsecurves from 10 μM to 1.87 nM) and compound transfer was performed usingthe ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well clear bottomassay plates (Greiner Bio-One) with appropriate DMSO backfill for afinal DMSO concentration of 0.1%. LL29 cells were plated at 1,500cells/well in 80 μl/well F12 medium supplemented with 1% Fetal BovineSerum. One hour after addition of the cells, TGF-β1 (Peprotech; 20ng/mL) was added to the plates to induce fibrosis (ref 1 and 2 above).Wells treated with TGF-β1 and containing DMSO were used as controls.Cells were incubated at 37° C. and 5% CO₂ for 4 days. Followingincubation for 4 days, SYTOX green nucleic acid stain (Life Technologies[Thermo Fisher Scientific]) was added to the wells at a finalconcentration of 1 uM and incubated at room temperature for 30 min.Cells were then fixed using 4% formaldehyde (Electron MicroscopySciences), washed 3 times with PBS followed by blocking andpermeabilization using 3% Bovine Serum Albumin (BSA; Sigma) and 0.3%Triton X-100 (Sigma) in PBS. Cells were then stained with antibodyspecific to α-smooth muscle actin (αSMA; Abcam) (ref 1 and 2 above) in3% Bovine Serum Albumin (BSA; Sigma) and 0.3% Triton X-100 (Sigma) inPBS, and incubated overnight at 4° C. Cells were then washed 3 timeswith PBS, followed by incubation with Alexa Flor-647 conjugatedsecondary antibody (Life Technologies [Thermo Fisher Scientific]) andDAPI at room temperature for 1 hour. Cells were then washed 3 times withPBS and plates were sealed for imaging. αSMA staining was imaged byexcitation at 630 nm and emission at 665 nm and quantified using theCompartmental Analysis program on the CellInsight CX5 (ThermoScientific). Dead or apoptotic cells were excluded from analysis basedon positive SYTOX green staining % of total cells positive for αSMA werecounted in each well and normalized to the average of 11 wells treatedwith TGF-β1 on the same plate using Dotmatics' Studies Software. Thenormalized averages (fold change over untreated) of 3 replicate wellsfor each compound concentration were used to create dose-responsescurves and EC₅₀ values were calculated using non-linear regression curvefit in the Dotmatics' Studies Software. The EC₅₀ values are reported.

Table 4 shows the activity of selected compounds as provided herein.

TABLE 4 Inhibition of fibrosis Compound EC₅₀ (μM) 1 0.009 7 0.017 130.009 20 0.010 25 0.048 28 0.741 34 0.047 40 0.078 46 0.094 52 0.147 550.009 61 0.081 68 1.672 73 1.189 82 0.009 87 0.124 90 0.009 93 0.009 1010.009 109 0.029 126 9.990 136 0.122 141 0.039 148 0.225 154 0.009 1570.099 169 0.009 175 0.187 181 0.009 184 0.277 190 0.009 196 0.009 2020.009 211 0.613 223 2.613 229 9.990 234 0.009 238 0.057 244 1.960 2500.258 265 0.009 268 0.009 269 0.049 271 0.009 277 0.009 283 0.009 2880.009 292 0.009 294 0.009 295 0.249 298 0.009 310 0.083 313 0.455 3200.096 321 0.306 325 0.009 329 0.067 331 0.029 337 0.009 352 9.990 3589.990 366 0.224 367 0.009 373 0.014 379 0.009 381 0.079 385 0.020 3920.267 394 0.110 400 0.218 412 9.176 421 0.009 424 0.051 427 0.009 4330.009 439 0.009 442 0.009 448 0.009 450 0.085 454 0.117 460 1.057 4660.308 937 9.990 939 0.009 947 9.990 948 0.072 949 9.990 952 9.990 9530.009 954 0.253 1350 0.009 1394 0.021

What is claimed is:
 1. A compound, or a pharmaceutically acceptable saltthereof, of Formula I:

wherein: R¹ is selected from the group consisting of -heteroaryl(R⁴)_(q)and -heterocyclyl(R⁵)_(h); R² is selected from the group consisting of Hand halide; R³ is selected from the group consisting of H,-heteroaryl(R⁶)_(q), -heterocyclyl(R⁷)_(h), and -aryl(R⁸)_(k); each R⁴is one substituent attached to the heteroaryl and is independentlyselected from the group consisting of halide, —(C₁₋₆ alkyl), —(C₁₋₄alkylene)_(p)heterocyclyl(R⁹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹¹)_(k),—NHC(═O)R¹², —NR¹³R¹⁴, —(C₁₋₆ alkylene)NR¹⁵R¹⁶, and —OR²²; each R⁵ isone substituent attached to the heterocyclyl and is independentlyselected from the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and—CN; each R⁶ is one substituent attached to the heteroaryl and isindependently selected from the group consisting of —(C₁₋₆ alkyl),halide, —CF₃, —OCH₃, —CN, and —C(═O)R¹⁷; each R⁷ is one substituentattached to the heterocyclyl and is independently selected from thegroup consisting of —(C₁₋₆ alkyl), halide, —CF₃, —CN, and —OCH₃; each R⁸is one substituent attached to the aryl and is independently selectedfrom the group consisting of —(C₁₋₆ alkyl), halide, —CF₃, —CN, —OCH₃,—(C₁₋₆ alkylene)_(p)NHSO₂R¹⁷, —NR¹³(C₁₋₆ alkylene)NR¹³R¹⁴, —(C₁₋₆alkylene)_(p)NR¹³R¹⁴, and —OR²⁵; each R⁹ is one substituent attached tothe heterocyclyl and is independently selected from the group consistingof amino, —(C₁₋₄ alkyl), halide, —CF₃, and —CN; each R¹⁰ is onesubstituent attached to the carbocyclyl and is independently selectedfrom the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and —CN; eachR¹¹ is one substituent attached to the aryl and is independentlyselected from the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and—CN; each R¹² is independently selected from the group consisting of—(C₁₋₉ alkyl), -heteroaryl(R¹⁸)_(q), -aryl(R¹⁹)_(k), —CH₂aryl(R¹⁹)_(k),-carbocyclyl(R²⁰)_(j), —CH₂carbocyclyl(R²⁰)_(j), —(C₁₋₄alkylene)_(p)NR²³R²⁴, -heterocyclyl(R²¹)_(h), and—CH₂heterocyclyl(R²¹)_(h); each R¹³ is independently selected from thegroup consisting of H and —(C₁₋₆ alkyl); each R¹⁴ is independentlyselected from the group consisting of H, —(C₁₋₆ alkyl),—CH₂aryl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j); each R¹⁵ isindependently selected from the group consisting of H and —(C₁₋₆ alkyl);each R¹⁶ is independently selected from the group consisting of H,—(C₁₋₆ alkyl), —CH₂aryl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j); each R¹⁷is a —(C₁₋₆ alkyl); each R¹⁸ is one substituent attached to theheteroaryl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN; each R¹⁹ is one substituentattached to the aryl and is independently selected from the groupconsisting of —(C₁₋₄ alkyl), halide, —CF₃, and —CN; each R²⁰ is onesubstituent attached to the carbocyclyl and is independently selectedfrom the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and —CN; eachR²¹ is one substituent attached to the heterocyclyl and is independentlyselected from the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and—CN; R²² is selected from the group consisting of H, —(C₁₋₆ alkyl),—(C₁₋₄ alkylene)_(p)heterocyclyl(R²¹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R²⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹⁹)_(k),and —(C₁₋₆ alkylene)_(p)NR²³R²⁴; each R²³ is independently selected fromthe group consisting of H and —(C₁₋₆ alkyl); each R²⁴ is independentlyselected from the group consisting of H and —(C₁₋₆ alkyl); R²⁵ isselected from the group consisting of H, —(C₁₋₆ alkyl), —(C₁₋₄alkylene)_(p)heterocyclyl(R²¹)_(h), and —(C₁₋₆ alkylene)_(p)NR²³R²⁴;each p is independently 0 or 1; each q is independently 0 to 4; each his independently 0 to 10; each k is independently 0 to 5; and each j isindependently 0 to
 12. 2. A pharmaceutical composition comprising acompound according to claim 1, or a pharmaceutically acceptable saltthereof, and a pharmaceutically acceptable excipient.
 3. The compound ofclaim 1, wherein R¹ is -heteroaryl(R⁴)_(q).
 4. The compound of claim 3,wherein R¹ is selected from the group consisting of -pyridinyl(R⁴)_(q),-pyrimidinyl(R⁴)_(q), -pyrazolyl(R⁴)_(q), and -imidazolyl(R⁴)_(q). 5.The compound of claim 3, wherein q is 0, 1 or
 2. 6. The compound ofclaim 3, wherein R⁴ is selected from the group consisting of —(C₁₋₃alkyl), —CH₂heterocyclyl(R⁹)_(h), —NHC(═O)R¹², —NR¹³R¹⁴, —CH₂NR¹⁵R¹⁶,and —OR²².
 7. The compound of claim 1, wherein R³ is -aryl(R⁸)_(k). 8.The compound of claim 7, wherein R³ is -phenyl(R⁸)_(k).
 9. The compoundof claim 7, wherein k is 1, or
 2. 10. The compound of claim 9, whereineach R⁸ is independently selected from the group consisting of halideand is —CH₂NHSO₂R¹⁷.
 11. The compound of claim 1, wherein R³ is-heteroaryl(R⁶)_(q).
 12. The compound of claim 11, wherein R³ isselected from the group consisting of -pyridinyl(R⁶)_(q),-imidazolyl(R⁶)_(q), -furanyl(R⁶)_(q), and -thiophenyl(R⁶)_(q).
 13. Thecompound of claim 11, wherein q is 0 or
 1. 14. The compound of claim 13,wherein q is 1 and R⁶ is selected from the group consisting of halide,—(C₁₋₃ alkyl), and —C(═O)R¹⁷.
 15. The compound of claim 1, wherein R³ is-heterocyclyl(R⁷)_(h).
 16. The compound of claim 15, wherein R³ isselected from the group consisting of -piperidinyl(R⁷)_(h),-morpholinyl(R⁷)_(h), and -piperazinyl(R⁷)_(h).
 17. The compound ofclaim 15, wherein h is 0, 1, or
 2. 18. The compound of claim 17, whereineach R⁷ is independently selected from the group consisting of a halideand —(C₁₋₃ alkyl).
 19. The compound of claim 1, wherein R² is H.
 20. Thecompound of claim 1, wherein the compound of Formula I is selected fromthe group consisting of:N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(1);N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(2);5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(3);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(4);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(5);N-((5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(6);5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N,N-dimethylpyridin-3-amine(7);N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(8);N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(9);N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(10);N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(11);5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N-isopropylpyridin-3-amine(12);1-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(13);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(14);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(15);N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide(16);N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(17);N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(18);N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(19);N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(20);N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(21);N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(22);N-benzyl-1-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(23);1-cyclopentyl-N-((5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(24);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(25);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(26);N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(27);N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(28);5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(29);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(30);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(31);N-((5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(32);5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N,N-dimethylpyridin-3-amine(33);N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(34);N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(35);N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(36);N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(37);5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N-isopropylpyridin-3-amine(38);1-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(39);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(40);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(41);N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide(42);N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(43);N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(44);N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(45);N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(46);N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(47);N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(48);N-benzyl-1-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(49);1-cyclopentyl-N-((5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(50);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(51);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(52);N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(53);N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(54);5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(55);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(56);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(57);N-((5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(58);5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N,N-dimethylpyridin-3-amine(59);N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(60);N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(61);N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(62);N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(63);5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N-isopropylpyridin-3-amine(64);1-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(65);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(66);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(67);N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide(68);N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(69);N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(70);N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(71);N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(72);N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(73);N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(74);N-benzyl-1-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(75);1-cyclopentyl-N-((5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(76);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(77);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(78);N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(79);3-methyl-N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(80);5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(81);5-(pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(82);5-(4-methylpyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(83);N-((5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(84);N,N-dimethyl-5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(85);N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(86);N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(87);2-phenyl-N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(88);N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(89);N-isopropyl-5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(90);N,N-dimethyl-1-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(91);3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(92);5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(93);3,3-dimethyl-N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(94);N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(95);N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(96);N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(97);N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(98);N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(99); andN-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(100); or a pharmaceutically acceptable salt thereof.
 21. The compoundof claim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-benzyl-1-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(101);1-cyclopentyl-N-((5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(102);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(103);3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(104);N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(105);3-methyl-N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(106);5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(107);5-(pyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(108);5-(4-methylpyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(109);N-((5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(110);N,N-dimethyl-5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(111);N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(112);N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(113);2-phenyl-N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(114);N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(115);N-isopropyl-5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(116);N,N-dimethyl-1-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(117);3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(118);5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(119);3,3-dimethyl-N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(120);N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(121);N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(122);N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(123);N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(124);N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(125);N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(126);N-benzyl-1-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(127);1-cyclopentyl-N-((5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(128);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(129);3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(130);N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(131);3-methyl-N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(132);5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(133);3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(134);5-(4-methylpyridin-3-yl)-3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(135);N-((5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(136);N,N-dimethyl-5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(137);N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(138);N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(139);2-phenyl-N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(140);N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(141);N-isopropyl-5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(142);N,N-dimethyl-1-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(143);3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(144);5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(145);3,3-dimethyl-N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(146);N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(147);N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(148);N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(149);N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(150);N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(151);N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(152);N-benzyl-1-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(153);1-cyclopentyl-N-((5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(154);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(155);3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(156);N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(157);3-methyl-N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(158);5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(159);3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(160);5-(4-methylpyridin-3-yl)-3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(161);N-((5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(162);N,N-dimethyl-5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(163);N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(164);N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(165);2-phenyl-N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(166);N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(167);N-isopropyl-5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(168);N,N-dimethyl-1-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(169);3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(170);3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(171);3,3-dimethyl-N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(172);N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(173);N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(174);N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(175);N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(176);N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(177);N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(178);N-benzyl-1-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(179);1-cyclopentyl-N-((5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(180);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(181);3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(182);N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(183);3-methyl-N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(184);5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(185);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(186);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(187);N-((5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(188);N,N-dimethyl-5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(189);N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(190);N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(191);N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(192);N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(193);N-isopropyl-5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(194);N,N-dimethyl-1-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(195);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(196);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(197);3,3-dimethyl-N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(198);N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(199); andN-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(200); or a pharmaceutically acceptable salt thereof.
 22. The compoundof claim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(201);N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(202);N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(203);N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(204);N-benzyl-1-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(205);1-cyclopentyl-N-((5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(206);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(207);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(208);N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(209);3-methyl-N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(210);5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(211);3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(212);3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(213);N-((5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(214);N,N-dimethyl-5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(215);N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(216);N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(217);N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(218);N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(219);N-isopropyl-5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(220);N,N-dimethyl-1-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(221);3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(222);3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(223);3,3-dimethyl-N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(224);N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(225);N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(226);N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(227);N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(228);N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(229);N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(230);N-benzyl-1-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(231);1-cyclopentyl-N-((5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(232); 5-(5-((3,3-difluoropyrrolidin-1-yl)-yl)methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(233);3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(234);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(235);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(236);5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(237);3-(1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(238);3-(1H-benzo[d]imidazol-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(239);N-((5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(240);5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N,N-dimethylpyridin-3-amine(241);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(242);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(243);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(244);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(245);5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N-isopropylpyridin-3-amine(246);1-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(247);3-(1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(248);3-(1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(249);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide(250);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(251);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(252);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(253);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(254);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(255);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(256);1-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-N-benzylmethanamine(257);1-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-N-(cyclopentylmethyl)methanamine(258);3-(1H-benzo[d]imidazol-2-yl)-5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(259);3-(1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(260);N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(261);3-methyl-N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(262);5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(263);5-(pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(264);5-(4-methylpyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(265);N-((5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(266);N,N-dimethyl-5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(267);N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(268);N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(269);2-phenyl-N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(270);N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(271);N-isopropyl-5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(272);N,N-dimethyl-1-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(273);5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(274);5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(275);3,3-dimethyl-N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(276);N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(277);N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(278);N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(279);N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(280);N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(281);N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(282);N-benzyl-1-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(283);1-cyclopentyl-N-((5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(284);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(285);5-(pyrimidin-5-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(286);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(287);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(288);5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(289);3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(290);3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(291);N-((5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(292);5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N,N-dimethylpyridin-3-amine(293);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(294);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(295);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(296);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(297);5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N-isopropylpyridin-3-amine(298);1-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(299); and3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(300); or a pharmaceutically acceptable salt thereof.
 23. The compoundof claim 1, wherein the compound of Formula I is selected from the groupconsisting of:3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(301);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide(302);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(303);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(304);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(305);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(306);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(307);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(308);N-benzyl-1-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(309);1-cyclopentyl-N-((5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(310);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(311);3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(312);N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(313);3-methyl-N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(314);5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(315);5-(pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(316);5-(4-methylpyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(317);N-((5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(318);N,N-dimethyl-5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(319);N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(320);N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(321);2-phenyl-N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(322);N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(323);N-isopropyl-5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(324);N,N-dimethyl-1-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(325);5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(326);5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(327);3,3-dimethyl-N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(328);N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(329);N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(330);N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(331);N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(332);N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(333);N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(334);N-benzyl-1-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(335);1-cyclopentyl-N-((5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(336);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(337);5-(pyrimidin-5-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(338);N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(339);N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(340);5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(341);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(342);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(343);N-((5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(344);5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N,N-dimethylpyridin-3-amine(345);N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(346);N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(347);N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(348);N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(349);5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N-isopropylpyridin-3-amine(350);1-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(351);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(352);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(353);N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide(354);N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(355);N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(356);N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(357);N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(358);N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(359);N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(360);N-benzyl-1-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(361);1-cyclopentyl-N-((5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(362);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(363);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(364);N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(365);3-methyl-N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(366);5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(367);3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(368);5-(4-methylpyridin-3-yl)-3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(369);N-((5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(370);N,N-dimethyl-5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(371);N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(372);N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(373);N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(374);N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(375);N-isopropyl-5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(376);N,N-dimethyl-1-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(377);3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(378);3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(379);3,3-dimethyl-N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butanamide(380);N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(381);N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(382);N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(383);N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(384);N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(385);N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(386);N-benzyl-1-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(387);1-cyclopentyl-N-((5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(388); 5-(5-((3,3-difluoropyrrolidin-1-yl)methy)pyridin-3-yl)-3-(4methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(389);3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(390);N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(391);N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(392);1-(5-(2-(5-(5-aminopyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(393);1-(5-(2-(5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(394);1-(5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(395);1-(5-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(396);1-(5-(2-(5-(5-(dimethylamino)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(397);N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(398);N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(399); andN-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(400); or a pharmaceutically acceptable salt thereof.
 24. The compoundof claim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(401);1-(5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(402);1-(5-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(403);1-(5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(404);1-(5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(405);N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide(406);N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(407);N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(408);N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(409);N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(410);N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(411);N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(412);1-(5-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(413);1-(5-(2-(5-(5-(((cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(414);1-(5-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(415);1-(5-(2-(5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(416);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(417);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(418);N-(3-(2-(5-(5-aminopyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide(419);N-(3-fluoro-5-(2-(5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(420);N-(3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(421);N-(3-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide(422);N-(3-(2-(5-(5-(dimethylamino)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide(423);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(424);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(425);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(426);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(427);N-(3-fluoro-5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(428);N-(3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide(429);N-(3-fluoro-5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(430);N-(3-fluoro-5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(431);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide(432);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(433);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(434);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(435);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(436);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(437);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(438);N-(3-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide(439);N-(3-(2-(5-(5-(((cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide(440);N-(3-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide(441);N-(3-fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(442);N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(443);N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(444);N¹-(3-(2-(5-(5-aminopyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(445);N¹-(3-fluoro-5-(2-(5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(446);N¹-(3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(447);N¹-(3-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(448);N¹-(3-(2-(5-(5-(dimethylamino)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(449);N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(450);N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(451);N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(452);N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(453);N¹-(3-fluoro-5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(454);N¹-(3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(455);N¹-(3-fluoro-5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(456);N¹-(3-fluoro-5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(457);N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide(458);N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(459);N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(460);N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(461);N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(462);N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(463);N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(464);N¹-(3-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(465);N¹-(3-(2-(5-(5-(((cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(466);N¹-(3-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(467); andN¹-(3-fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(468); or a pharmaceutically acceptable salt thereof.
 25. The compoundof claim 1, wherein the compound of Formula I is selected from the groupconsisting of:3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridine(937);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(938);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(939);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(940);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(941);1-(6-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(942);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(943);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(944);N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(945);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(946);2-((5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine(947);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(948);5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(949);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(950);2-cyclohexyl-N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(951);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(952);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine(953);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridine(954);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridine(955);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(956);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(957);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(958);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(959);1-(6-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(960);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(961);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(962);N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(963);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(964);2-((5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine(965);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(966);5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(967);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(968);2-cyclohexyl-N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(969);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(970);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine(971);3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridine(972);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridine(973);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(974);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(975);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(976);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(977);1-(6-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(978);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(979);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(980);N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(981);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(982);2-((5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine(983);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(984);5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(985);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(986);2-cyclohexyl-N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(987);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(988);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine(989);3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridine(990);5-(piperidin-4-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(991);3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(992);5-(1H-pyrazol-4-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(993);5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(994);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(995);1-(6-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(996);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(997);5-(5-(piperidin-4-yloxy)pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(998);2-(piperidin-4-yl)-N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(999); and3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1000); or a pharmaceutically acceptable salt thereof.
 26. The compoundof claim 1, wherein the compound of Formula I is selected from the groupconsisting of:N,N-dimethyl-2-((5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine(1001);5-(5-methoxypyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1002);5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1003);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1004);2-cyclohexyl-N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1005);3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1006);5-(pyridin-2-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1007);5-(pyrazin-2-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1108);5-(piperidin-4-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1009);3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1010);5-(1H-pyrazol-4-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1011);5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1012);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1013);1-(6-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(1014);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1015);5-(5-(piperidin-4-yloxy)pyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1016);2-(piperidin-4-yl)-N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1017);3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1018);N,N-dimethyl-2-((5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine(1019);5-(5-methoxypyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1020);5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1021);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1022);2-cyclohexyl-N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1023);5-(pyridin-4-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1024);5-(pyridin-2-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1025);5-(pyrazin-2-yl)-3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1026);5-(piperidin-4-yl)-3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1027);3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1028);5-(1H-pyrazol-4-yl)-3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1029);5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1030);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1031);1-(6-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(1032);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1033);5-(5-(piperidin-4-yloxy)pyridin-3-yl)-3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1034);2-(piperidin-4-yl)-N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1035);3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1036);N,N-dimethyl-2-((5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine(1037);5-(5-methoxypyridin-3-yl)-3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1038);5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1039);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1040);2-cyclohexyl-N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1041);3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1042);5-(pyridin-2-yl)-3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1043);5-(pyrazin-2-yl)-3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1044);3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1045);3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1046);3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1047);5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1048);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1049);1-(6-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(1050);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(piperidin-1-yl)-1H-benzo[d]imidazo-1-yl)-1H-pyrazolo[3,4-c]pyridine(1051);3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1052);N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(1053);3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1054);N,N-dimethyl-2-((5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine(1055);5-(5-methoxypyridin-3-yl)-3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1056);5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1057);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1058);2-cyclohexyl-N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1059);3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1060);3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1061);3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1062);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1063);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1064);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1065);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1066);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1067);1-(6-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(1068);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1069);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1070);N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(1071);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1072);N,N-dimethyl-2-((5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine(1073);5-(5-methoxypyridin-3-yl)-3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1074);5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1075);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1076);2-cyclohexyl-N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1077);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1078);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1079);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1080);3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1081);3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1082);3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1083);5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1084);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1085);1-(6-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(1086);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1087);3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1088);N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(1089);3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1090);N,N-dimethyl-2-((5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine(1091);5-(5-methoxypyridin-3-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1092);5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1093);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1094);2-cyclohexyl-N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1095);3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1096);3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1097);3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1098);3-(1H-benzo[d]imidazol-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1099); and3-(1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1100); or a pharmaceutically acceptable salt thereof.
 27. The compoundof claim 1, wherein the compound of Formula I is selected from the groupconsisting of:3-(1H-benzo[d]imidazol-2-yl)-5-(H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1101);3-(1H-benzo[d]imidazol-2-yl)-5-(1-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1102);3-(1H-benzo[d]imidazol-2-yl)-5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-c]pyridine(1103);1-(6-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(1104);3-(1H-benzo[d]imidazol-2-yl)-5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1105);3-(1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1106);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(1107);3-(1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1108);2-((5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine(1109);3-(1H-benzo[d]imidazol-2-yl)-5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1110);5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1111);3-(1H-benzo[d]imidazol-2-yl)-5-(5-(benzyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1112);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-cyclohexylacetamide(1113);3-(1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1114);3-(1H-benzo[d]imidazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1115);3-(1H-benzo[d]imidazol-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1116);5-(piperidin-4-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1117);5-(1,2,3,6-tetrahydropyridin-4-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1118);5-(1H-pyrazol-4-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1119);5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1120);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1121);1-(6-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(1122);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1123);5-(5-(piperidin-4-yloxy)pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1124);2-(piperidin-4-yl)-N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1125);5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1126);N,N-dimethyl-2-((5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine(1127);5-(5-methoxypyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1128);5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1129);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1130);2-cyclohexyl-N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1131);5-(pyridin-4-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1132);5-(pyridin-2-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1133);5-(pyrazin-2-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1134);3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1135);3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1136);3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1137);3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1138);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1139);1-(6-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(1140);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1141);3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1142);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(1143);3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1144);2-((5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine(1145);3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1146);5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1147);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1148);2-cyclohexyl-N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1149);3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1150);3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1151);3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1152);5-(piperidin-4-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1153);5-(1,2,3,6-tetrahydropyridin-4-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1154);5-(1H-pyrazol-4-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1155);5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1156);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1157);1-(6-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(1158);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1159);5-(5-(piperidin-4-yloxy)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1160);2-(piperidin-4-yl)-N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1161);5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1162);N,N-dimethyl-2-((5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine(1163);5-(5-methoxypyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1164);5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1165);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1166);2-cyclohexyl-N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1167);5-(pyridin-4-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1168);5-(pyridin-2-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1169);5-(pyrazin-2-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1170);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1171);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1172);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1173);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1174);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1175);1-(6-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(1176);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1177);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1178);N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(1179);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1180);2-((5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine(1181);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1182);5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1183);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1184);2-cyclohexyl-N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1185);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1186);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1187);3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1188);3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1189);3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1190);3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1191);5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1192);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1193);1-(6-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(1194);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1195);3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1196);N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(1197);3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1198);N,N-dimethyl-2-((5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine(1199); and5-(5-methoxypyridin-3-yl)-3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1200); or a pharmaceutically acceptable salt thereof.
 28. The compoundof claim 1, wherein the compound of Formula I is selected from the groupconsisting of:5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1201);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1202);2-cyclohexyl-N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1203);3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1204);3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1205);3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1206);1-(5-(2-(5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1207);1-(5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1208);1-(5-(2-(5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1209);1-(5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1210);1-(5-(2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1211);1-(5-(2-(5-(6-(3-aminoazetidin-1-yl)pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1212);1-(5-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1213);1-(5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1214);N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(1215);1-(5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1216);1-(5-(2-(5-(5-(2-(dimethylamino)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1217);1-(5-(2-(5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1218);1-(5-(2-(5-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1219);1-(5-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1220);N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-cyclohexylacetamide(1221);1-(5-(2-(5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1222);1-(5-(2-(5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1223);1-(5-(2-(5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)thiophen-2-yl)ethan-1-one(1224);N-(3-fluoro-5-(2-(5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(1225);N-(3-fluoro-5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(1226);N-(3-(2-(5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide(1227);N-(3-fluoro-5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(1228);N-(3-(2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide(1229);N-(3-(2-(5-(6-(3-aminoazetidin-1-yl)pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide(1230);N-(3-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide(1231);N-(3-fluoro-5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(1232);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(1233);N-(3-fluoro-5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(1234);N-(3-(2-(5-(5-(2-(dimethylamino)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide(1235);N-(3-fluoro-5-(2-(5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(1236);N-(3-fluoro-5-(2-(5-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(1237);N-(3-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide(1238);2-cyclohexyl-N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1239);N-(3-fluoro-5-(2-(5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(1240);N-(3-fluoro-5-(2-(5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(1241);N-(3-fluoro-5-(2-(5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(1242);N¹-(3-fluoro-5-(2-(5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(1243);N¹-(3-fluoro-5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(1244);N¹-(3-(2-(5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(1245);N¹-(3-fluoro-5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(1246);N¹-(3-(2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(1247);N¹-(3-(2-(5-(6-(3-aminoazetidin-1-yl)pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(1248);N¹-(3-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(1249);N¹-(3-fluoro-5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(1250);N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(1251);N¹-(3-fluoro-5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(1252);N¹-(3-(2-(5-(5-(2-(dimethylamino)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(1253);N¹-(3-fluoro-5-(2-(5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(1254);5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1255);N¹-(3-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(1256);2-cyclohexyl-N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1257);N¹-(3-fluoro-5-(2-(5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(1258);N¹-(3-fluoro-5-(2-(5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(1259);N¹-(3-fluoro-5-(2-(5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(1260);N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(1261);N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(1262);5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(1263);2-(3-fluoro-5-(2-(5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenoxy)-N,N-dimethylethan-1-amine(1264);2-(3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenoxy)-N,N-dimethylethan-1-amine(1265);2-(3-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine(1266);5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N,N-dimethylpyridin-3-amine(1267);N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(1268);N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(1269);N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(1270);N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(1271);5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N-isopropylpyridin-3-amine(1272);2-(3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine(1273);2-(3-fluoro-5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenoxy)-N,N-dimethylethan-1-amine(1274);2-(3-fluoro-5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenoxy)-N,N-dimethylethan-1-amine(1275);N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide(1276);N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(1277);N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(1278);N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(1279);N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(1280);N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(1281);N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(1282);2-(3-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine(1283);2-(3-(2-(5-(5-(((cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine(1284);2-(3-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine(1285);2-(3-fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenoxy)-N,N-dimethylethan-1-amine(1286);2-(3-fluoro-5-(2-(5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenoxy)-N,N-dimethylethan-1-amine(1287);2-(3-fluoro-5-(2-(5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenoxy)-N,N-dimethylethan-1-amine(1288);2-(3-fluoro-5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenoxy)-N,N-dimethylethan-1-amine(1289);2-(3-(2-(5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine(1290);2-(3-fluoro-5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenoxy)-N,N-dimethylethan-1-amine(1291);2-(3-(2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine(1292);1-(6-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(1293);2-(3-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine(1294);2-(3-fluoro-5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenoxy)-N,N-dimethylethan-1-amine(1295);N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(1296);2-(3-fluoro-5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenoxy)-N,N-dimethylethan-1-amine(1297);2-((5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine(1298);2-(3-fluoro-5-(2-(5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenoxy)-N,N-dimethylethan-1-amine(1299); and5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1300); or a pharmaceutically acceptable salt thereof.
 29. The compoundof claim 1, wherein the compound of Formula I is selected from the groupconsisting of:2-(3-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine(1301);2-cyclohexyl-N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1302);2-(3-fluoro-5-(2-(5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenoxy)-N,N-dimethylethan-1-amine(1303);2-(3-fluoro-5-(2-(5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenoxy)-N,N-dimethylethan-1-amine(1304);N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(1305);N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(1306);5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(1307);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1308);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1309);N-((5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(1310);5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N,N-dimethylpyridin-3-amine(1311);N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(1312);N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(1313);N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(1314);N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(1315);5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N-isopropylpyridin-3-amine(1316);1-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(1317);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1318);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1319);N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide(1320);N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(1321);N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(1322);N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(1323);N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(1324);N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(1325);N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(1326);N-benzyl-1-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(1327);1-cyclopentyl-N-((5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(1328);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1329);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(1330);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1331);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1332);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1333);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1334);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1335);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1336);1-(6-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(1337);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1338);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1339);N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(1340);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1341);2-((5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine(1342);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1343);5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1344);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1345);2-cyclohexyl-N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1346);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1347);3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1348);N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(1349);N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(1350);3-(2-(5-(5-aminopyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenol(1351);3-fluoro-5-(2-(5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1352);3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1353);3-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenol(1354);3-(2-(5-(5-(dimethylamino)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenol(1355);N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(1356);N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(1357);N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(1358);N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(1359);3-fluoro-5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1360);3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenol(1361);3-fluoro-5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1362);3-fluoro-5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1363);N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide(1364);N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(1365);N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(1366);N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(1367);N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(1368);N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(1369);N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(1370);3-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenol(1371);3-(2-(5-(5-(((cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenol(1372);3-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenol(1373);3-fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1374);3-fluoro-5-(2-(5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1375);3-fluoro-5-(2-(5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1376);3-fluoro-5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1377);3-(2-(5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenol(1378);3-fluoro-5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1379);3-(2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenol(1380);3-(2-(5-(6-(3-aminoazetidin-1-yl)pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenol(1381);3-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenol(1382);3-fluoro-5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1383);N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(1384);3-fluoro-5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1385);3-(2-(5-(5-(2-(dimethylamino)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenol(1386);3-fluoro-5-(2-(5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1387);5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1388);3-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenol(1389);2-cyclohexyl-N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1390);3-fluoro-5-(2-(5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1391);3-fluoro-5-(2-(5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)phenol(1392);N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(1393);N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(1394);5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(1395);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1396);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1397);N-((5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(1398);5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N,N-dimethylpyridin-3-amine(1399); andN-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(1400); or a pharmaceutically acceptable salt thereof.
 30. The compoundof claim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)isobutyramide(1401);N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide(1402);N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(1403);5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N-isopropylpyridin-3-amine(1404);1-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(1405);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1406);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1407);N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide(1408);N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(1409);N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pentanamide(1410);N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide(1411]N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(1412);N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide(1413);N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide(1414);N-benzyl-1-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(1415);1-cyclopentyl-N-((5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(1416);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1417);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(1418);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1419);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1420);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1421);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1422);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1423);5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1424);1-(6-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine(1425);5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1426);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1427);N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide(1428);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1429);2-((5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine(1430);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1431);5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-ol(1432);5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1433);2-cyclohexyl-N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1434);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridine(1435);3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridine(1436);2-(dimethylamino)-N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1437);2-(dimethylamino)-N-(5-(3-(4-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1438);2-(dimethylamino)-N-(5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1439);2-(dimethylamino)-N-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1440);2-(dimethylamino)-N-(5-(3-(4-(pyridin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1441);2-(dimethylamino)-N-(5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1442);2-(dimethylamino)-N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1443);2-(dimethylamino)-N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1444);2-(dimethylamino)-N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1445);N-(5-(3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(dimethylamino)acetamide(1446);2-(dimethylamino)-N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1447);2-(dimethylamino)-N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1448);2-(dimethylamino)-N-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1449);2-(dimethylamino)-N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1450);2-(dimethylamino)-N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1451);N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-2-(dimethylamino)acetamide(1452);2-(dimethylamino)-N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1453);2-(dimethylamino)-N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1454);2-(dimethylamino)-N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1455);2-(dimethylamino)-N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1456);2-(dimethylamino)-N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1457);2-(dimethylamino)-N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)acetamide(1458);4-(2-(5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)morpholine(1459);3-(4-(4,4-difluoropiperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1460);3-(4-(1-methylpiperidin-4-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1461);4-(2-(5-(5-fluoropyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)morpholine (1462);5-(5-fluoropyridin-3-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1463);3-(4-(4,4-difluoropiperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-fluoropyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(1464);5-(5-fluoropyridin-3-yl)-3-(4-(1-methylpiperidin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1465);5-(5-fluoropyridin-3-yl)-3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1466);4-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)morpholine (1467);3-(4-(4,4-difluoropiperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1468);5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(1-methylpiperidin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1469);4-(2-(5-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)morpholine(1470);5-(1-cyclopropyl-1H-pyrazol-4-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1471);5-(1-cyclopropyl-1H-pyrazol-4-yl)-3-(4-(4,4-difluoropiperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1472);5-(1-cyclopropyl-1H-pyrazol-4-yl)-3-(4-(1-methylpiperidin-4-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1473);5-(1-cyclopropyl-1H-pyrazol-4-yl)-3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(1473);4-(2-(5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)morpholine (1474);3-(4-(4,4-difluoropiperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1475); and3-(4-(1-methylpiperidin-4-yl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(1476); or a pharmaceutically acceptable salt thereof.
 31. The compoundof claim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(1);1-(5-(3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine(13);5-(3-(4-(2-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(55);5-(pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(82);N-isopropyl-5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine(90);5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(93);N-benzyl-1-(5-(3-(4-(pyridin-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(101);1-cyclopentyl-N-((5-(3-(4-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)methanamine(154);N-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)propionamide(157);N,N-dimethyl-1-(5-(3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(169);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(piperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(181);N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(190);3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine(196);N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide(202);3-(4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridine(234);5-(4-methylpyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine(265);N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(268);N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(271);N-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(277);N-benzyl-1-(5-(3-(4-(thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine(283);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(288);N-((5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine(292);N-(5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)pivalamide(294);5-(3-(4-(furan-3-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N-isopropylpyridin-3-amine(298);N,N-dimethyl-1-(5-(3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)methanamine[325);5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridine[337);5-(3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-amine[367);3-(4-(5-methylthiophen-2-yl)-1H-benzo[d]imidazol-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine[379);N-(3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(421);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)benzamide(427);N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)butyramide(433);N-(3-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorobenzyl)methanesulfonamide(439);N-(3-fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)benzyl)methanesulfonamide(442);N¹-(3-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-benzo[d]imidazol-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(448);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine(939);3-(4-(3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine(953); andN-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide(1350); or a pharmaceutically acceptable salt thereof.
 32. The compoundof claim 1, wherein the compound of Formula I is selected from the groupconsisting of:

or a pharmaceutically acceptable salt thereof.